RNA sequestration in P-bodies sustains myeloid leukaemia.


Journal

Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575

Informations de publication

Date de publication:
21 Aug 2024
Historique:
received: 18 09 2023
accepted: 18 07 2024
medline: 22 8 2024
pubmed: 22 8 2024
entrez: 21 8 2024
Statut: aheadofprint

Résumé

Post-transcriptional mechanisms are fundamental safeguards of progenitor cell identity and are often dysregulated in cancer. Here, we identified regulators of P-bodies as crucial vulnerabilities in acute myeloid leukaemia (AML) through genome-wide CRISPR screens in normal and malignant haematopoietic progenitors. We found that leukaemia cells harbour aberrantly elevated numbers of P-bodies and show that P-body assembly is crucial for initiation and maintenance of AML. Notably, P-body loss had little effect upon homoeostatic haematopoiesis but impacted regenerative haematopoiesis. Molecular characterization of P-bodies purified from human AML cells unveiled their critical role in sequestering messenger RNAs encoding potent tumour suppressors from the translational machinery. P-body dissolution promoted translation of these mRNAs, which in turn rewired gene expression and chromatin architecture in leukaemia cells. Collectively, our findings highlight the contrasting and unique roles of RNA sequestration in P-bodies during tissue homoeostasis and oncogenesis. These insights open potential avenues for understanding myeloid leukaemia and future therapeutic interventions.

Identifiants

pubmed: 39169219
doi: 10.1038/s41556-024-01489-6
pii: 10.1038/s41556-024-01489-6
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Cancer Prevention and Research Institute of Texas (Cancer Prevention Research Institute of Texas)
ID : RR200079
Organisme : Cancer Prevention and Research Institute of Texas (Cancer Prevention Research Institute of Texas)
ID : RR200040
Organisme : U.S. Department of Health & Human Services | NIH | Office of Extramural Research, National Institutes of Health (OER)
ID : 1R35GM147126-01
Organisme : U.S. Department of Health & Human Services | NIH | Office of Extramural Research, National Institutes of Health (OER)
ID : 1F32CA288043-01
Organisme : U.S. Department of Health & Human Services | NIH | Office of Extramural Research, National Institutes of Health (OER)
ID : 5T32DK060445-19
Organisme : Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)
ID : CP22/00127
Organisme : Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)
ID : CP19/00176
Organisme : Worldwide Cancer Research
ID : 20-0269
Pays : United Kingdom
Organisme : Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung)
ID : P-35628
Organisme : Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung)
ID : P35298

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer Nature Limited.

Références

van Galen, P. et al. Single-cell RNA-seq reveals AML hierarchies relevant to disease progression and immunity. Cell 176, 1265–1281 e1224 (2019).
pubmed: 30827681 pmcid: 6515904 doi: 10.1016/j.cell.2019.01.031
Fabbri, L., Chakraborty, A., Robert, C. & Vagner, S. The plasticity of mRNA translation during cancer progression and therapy resistance. Nat. Rev. Cancer 21, 558–577 (2021).
pubmed: 34341537 doi: 10.1038/s41568-021-00380-y
Buxbaum, A. R., Haimovich, G. & Singer, R. H. In the right place at the right time: visualizing and understanding mRNA localization. Nat. Rev. Mol. Cell Biol. 16, 95–109 (2015).
pubmed: 25549890 doi: 10.1038/nrm3918
Roden, C. & Gladfelter, A. S. RNA contributions to the form and function of biomolecular condensates. Nat. Rev. Mol. Cell Biol. 22, 183–195 (2021).
pubmed: 32632317 doi: 10.1038/s41580-020-0264-6
Sheth, U. & Parker, R. Decapping and decay of messenger RNA occur in cytoplasmic processing bodies. Science 300, 805–808 (2003).
pubmed: 12730603 pmcid: 1876714 doi: 10.1126/science.1082320
Courel, M. et al. GC content shapes mRNA storage and decay in human cells. eLife 8, e49708 (2019).
pubmed: 31855182 pmcid: 6944446 doi: 10.7554/eLife.49708
Brengues, M., Teixeira, D. & Parker, R. Movement of eukaryotic mRNAs between polysomes and cytoplasmic processing bodies. Science 310, 486–489 (2005).
pubmed: 16141371 pmcid: 1863069 doi: 10.1126/science.1115791
Di Stefano, B. et al. The RNA helicase DDX6 controls cellular plasticity by modulating P-body homeostasis. Cell Stem Cell 25, 622–638 e613 (2019).
pubmed: 31588046 pmcid: 7247364 doi: 10.1016/j.stem.2019.08.018
Hubstenberger, A. et al. P-body purification reveals the condensation of repressed mRNA regulons. Mol. Cell 68, 144–157 e145 (2017).
pubmed: 28965817 doi: 10.1016/j.molcel.2017.09.003
Teixeira, D., Sheth, U., Valencia-Sanchez, M. A., Brengues, M. & Parker, R. Processing bodies require RNA for assembly and contain nontranslating mRNAs. RNA 11, 371–382 (2005).
pubmed: 15703442 pmcid: 1370727 doi: 10.1261/rna.7258505
Ayache, J. et al. P-body assembly requires DDX6 repression complexes rather than decay or Ataxin2/2L complexes. Mol. Biol. Cell 26, 2579–2595 (2015).
pubmed: 25995375 pmcid: 4501357 doi: 10.1091/mbc.E15-03-0136
Wilbertz, J. H. et al. Single-molecule imaging of mRNA localization and regulation during the integrated stress response. Mol. Cell 73, 946–958 e947 (2019).
pubmed: 30661979 doi: 10.1016/j.molcel.2018.12.006
Cardona, A. H. et al. Self-demixing of mRNA copies buffers mRNA:mRNA and mRNA:regulator stoichiometries. Cell 186, 4310–4324 e4323 (2023).
pubmed: 37703874 doi: 10.1016/j.cell.2023.08.018
Hallacli, E. et al. The Parkinson’s disease protein alpha-synuclein is a modulator of processing bodies and mRNA stability. Cell 185, 2035–2056 e2033 (2022).
pubmed: 35688132 pmcid: 9394447 doi: 10.1016/j.cell.2022.05.008
Lavalee, M., Curdy, N., Laurent, C., Fournie, J. J. & Franchini, D. M. Cancer cell adaptability: turning ribonucleoprotein granules into targets. Trends Cancer 7, 902–915 (2021).
pubmed: 34144941 doi: 10.1016/j.trecan.2021.05.006
Nsengimana, B. et al. Processing body (P-body) and its mediators in cancer. Mol. Cell. Biochem. 477, 1217–1238 (2022).
pubmed: 35089528 doi: 10.1007/s11010-022-04359-7
Ghashghaei, M. et al. miR-148a-3p and DDX6 functional link promotes survival of myeloid leukemia cells. Blood Adv. 7, 3846–3861 (2023).
pubmed: 36322827 doi: 10.1182/bloodadvances.2022008123
Hernandez, G. et al. Decapping protein EDC4 regulates DNA repair and phenocopies BRCA1. Nat. Commun. 9, 967 (2018).
pubmed: 29511213 pmcid: 5840268 doi: 10.1038/s41467-018-03433-3
Heyes, E. et al. Identification of gene targets of mutant C/EBPα reveals a critical role for MSI2 in CEBPA-mutated AML. Leukemia 35, 2526–2538 (2021).
pubmed: 33623142 pmcid: 7611617 doi: 10.1038/s41375-021-01169-6
Brandstoetter, T. et al. SBNO2 is a critical mediator of STAT3-driven hematological malignancies. Blood https://doi.org/10.1182/blood.2022018494 (2023).
Luo, Y., Na, Z. & Slavoff, S. A. P-bodies: composition, properties, and functions. Biochemistry 57, 2424–2431 (2018).
pubmed: 29381060 doi: 10.1021/acs.biochem.7b01162
Consortium, E. P. An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57–74 (2012).
doi: 10.1038/nature11247
Rasch, F., Weber, R., Izaurralde, E. & Igreja, C. 4E-T-bound mRNAs are stored in a silenced and deadenylated form. Genes Dev. 34, 847–860 (2020).
pubmed: 32354837 pmcid: 7263148 doi: 10.1101/gad.336073.119
Kamenska, A. et al. The DDX6-4E-T interaction mediates translational repression and P-body assembly. Nucleic Acids Res. 44, 6318–6334 (2016).
pubmed: 27342281 pmcid: 5291280 doi: 10.1093/nar/gkw565
Zong, H. et al. A hyperactive signalosome in acute myeloid leukemia drives addiction to a tumor-specific Hsp90 species. Cell Rep. 13, 2159–2173 (2015).
pubmed: 26628369 pmcid: 4699804 doi: 10.1016/j.celrep.2015.10.073
Nakagawa, T. et al. Establishment of a leukaemic cell line from a patient with acquisition of chromosomal abnormalities during disease progression in myelodysplastic syndrome. Br. J. Haematol. 85, 469–476 (1993).
pubmed: 8136267 doi: 10.1111/j.1365-2141.1993.tb03334.x
Erb, M. A. et al. Transcription control by the ENL YEATS domain in acute leukaemia. Nature 543, 270–274 (2017).
pubmed: 28241139 pmcid: 5497220 doi: 10.1038/nature21688
Yan, M. et al. A previously unidentified alternatively spliced isoform of t(8;21) transcript promotes leukemogenesis. Nat. Med. 12, 945–949 (2006).
pubmed: 16892037 doi: 10.1038/nm1443
Kim, J. et al. The RNA helicase DDX6 controls early mouse embryogenesis by repressing aberrant inhibition of BMP signaling through miRNA-mediated gene silencing. PLoS Genet. 18, e1009967 (2022).
pubmed: 36197846 pmcid: 9534413 doi: 10.1371/journal.pgen.1009967
Doulatov, S. et al. Induction of multipotential hematopoietic progenitors from human pluripotent stem cells via respecification of lineage-restricted precursors. Cell Stem Cell 13, 459–470 (2013).
pubmed: 24094326 doi: 10.1016/j.stem.2013.09.002
Brzezinka, K. et al. Functional diversity of inhibitors tackling the differentiation blockage of MLL-rearranged leukemia. J. Hematol. Oncol. 12, 66 (2019).
pubmed: 31253180 pmcid: 6599250 doi: 10.1186/s13045-019-0749-y
Hong, Y., Martin, J. F., Vainchenker, W. & Erusalimsky, J. D. Inhibition of protein kinase C suppresses megakaryocytic differentiation and stimulates erythroid differentiation in HEL cells. Blood 87, 123–131 (1996).
pubmed: 8547633 doi: 10.1182/blood.V87.1.123.123
Stein, E. M. et al. The DOT1L inhibitor pinometostat reduces H3K79 methylation and has modest clinical activity in adult acute leukemia. Blood 131, 2661–2669 (2018).
pubmed: 29724899 pmcid: 6265654 doi: 10.1182/blood-2017-12-818948
Jangra, R. K., Yi, M. & Lemon, S. M. DDX6 (Rck/p54) is required for efficient hepatitis C virus replication but not for internal ribosome entry site-directed translation. J. Virol. 84, 6810–6824 (2010).
pubmed: 20392846 pmcid: 2903299 doi: 10.1128/JVI.00397-10
Brandmann, T. et al. Molecular architecture of LSM14 interactions involved in the assembly of mRNA silencing complexes. EMBO J. 37, e97869 (2018).
pubmed: 29510985 pmcid: 5881628 doi: 10.15252/embj.201797869
Brothers, W. R., Fakim, H., Kajjo, S. & Fabian, M. R. P-bodies directly regulate MARF1-mediated mRNA decay in human cells. Nucleic Acids Res. 50, 7623–7636 (2022).
pubmed: 35801873 pmcid: 9303261 doi: 10.1093/nar/gkac557
Na, Z. et al. The NBDY microprotein regulates cellular RNA decapping. Biochemistry 59, 4131–4142 (2020).
pubmed: 33059440 doi: 10.1021/acs.biochem.0c00672
Na, Z. et al. Phosphorylation of a human microprotein promotes dissociation of biomolecular condensates. J. Am. Chem. Soc. 143, 12675–12687 (2021).
pubmed: 34346674 pmcid: 8564862 doi: 10.1021/jacs.1c05386
D’Lima, N. G. et al. A human microprotein that interacts with the mRNA decapping complex. Nat. Chem. Biol. 13, 174–180 (2017).
pubmed: 27918561 doi: 10.1038/nchembio.2249
Ren, Z. et al. A PRC2-Kdm5b axis sustains tumorigenicity of acute myeloid leukemia. PNAS 119, e2122940119 (2022).
pubmed: 35217626 pmcid: 8892512 doi: 10.1073/pnas.2122940119
Wong, S. H. et al. The H3K4-methyl epigenome regulates leukemia stem cell oncogenic potential. Cancer Cell 28, 198–209 (2015).
pubmed: 26190263 pmcid: 4536132 doi: 10.1016/j.ccell.2015.06.003
Muto, T. et al. TRAF6 functions as a tumor suppressor in myeloid malignancies by directly targeting MYC oncogenic activity. Cell Stem Cell 29, 298–314 e299 (2022).
pubmed: 35045331 pmcid: 8822959 doi: 10.1016/j.stem.2021.12.007
Gudgeon, C. J. et al. High expression of neutrophil elastase predicts improved survival in pediatric acute myeloid leukemia: a report from the Children’s Oncology Group. Leuk. Lymphoma 54, 202–204 (2013).
pubmed: 22680764 doi: 10.3109/10428194.2012.700480
Perner, F. et al. YBX1 mediates translation of oncogenic transcripts to control cell competition in AML. Leukemia 36, 426–437 (2022).
pubmed: 34465866 doi: 10.1038/s41375-021-01393-0
Jiang, L. et al. Multidimensional study of the heterogeneity of leukemia cells in t(8;21) acute myelogenous leukemia identifies the subtype with poor outcome. PNAS 117, 20117–20126 (2020).
pubmed: 32747558 pmcid: 7443908 doi: 10.1073/pnas.2003900117
Van Nostrand, E. L. et al. Robust transcriptome-wide discovery of RNA-binding protein binding sites with enhanced CLIP (eCLIP). Nat. Methods 13, 508–514 (2016).
pubmed: 27018577 pmcid: 4887338 doi: 10.1038/nmeth.3810
Sloan, K. E. & Bohnsack, M. T. Unravelling the mechanisms of RNA helicase regulation. Trends Biochem. Sci. 43, 237–250 (2018).
pubmed: 29486979 doi: 10.1016/j.tibs.2018.02.001
Chan, S. P. & Slack, F. J. microRNA-mediated silencing inside P-bodies. RNA Biol. 3, 97–100 (2006).
pubmed: 17179742 doi: 10.4161/rna.3.3.3499
Freimer, J. W., Hu, T. J. & Blelloch, R. Decoupling the impact of microRNAs on translational repression versus RNA degradation in embryonic stem cells. eLife 7, e38014 (2018).
pubmed: 30044225 pmcid: 6086665 doi: 10.7554/eLife.38014
Kulkarni, M., Ozgur, S. & Stoecklin, G. On track with P-bodies. Biochem. Soc. Trans. 38, 242–251 (2010).
pubmed: 20074068 doi: 10.1042/BST0380242
Xue, S. et al. Histone lysine demethylase KDM5B maintains chronic myeloid leukemia via multiple epigenetic actions. Exp. Hematol. 82, 53–65 (2020).
pubmed: 32007477 doi: 10.1016/j.exphem.2020.01.006
Patel, K. P. et al. Acute myeloid leukemia with IDH1 or IDH2 mutation: frequency and clinicopathologic features. Am. J. Clin. Pathol. 135, 35–45 (2011).
pubmed: 21173122 doi: 10.1309/AJCPD7NR2RMNQDVF
Bluemn, T. et al. Differential roles of BAF and PBAF subunits, Arid1b and Arid2, in MLL-AF9 leukemogenesis. Leukemia 36, 946–955 (2022).
pubmed: 35022500 pmcid: 10095935 doi: 10.1038/s41375-021-01505-w
Fog, C. K. et al. Loss of PRDM11 promotes MYC-driven lymphomagenesis. Blood 125, 1272–1281 (2015).
pubmed: 25499759 doi: 10.1182/blood-2014-03-560805
Horak, P. et al. TUSC3 loss alters the ER stress response and accelerates prostate cancer growth in vivo. Sci. Rep. 4, 3739 (2014).
pubmed: 24435307 pmcid: 3894551 doi: 10.1038/srep03739
Katerndahl, C. D. S. et al. Tumor suppressor function of Gata2 in acute promyelocytic leukemia. Blood 138, 1148–1161 (2021).
pubmed: 34125173 pmcid: 8570055 doi: 10.1182/blood.2021011758
Yu, J. S. et al. PCDH8, the human homolog of PAPC, is a candidate tumor suppressor of breast cancer. Oncogene 27, 4657–4665 (2008).
pubmed: 18408767 pmcid: 3013056 doi: 10.1038/onc.2008.101
Konopleva, M. & Letai, A. BCL-2 inhibition in AML: an unexpected bonus? Blood 132, 1007–1012 (2018).
pubmed: 30037885 pmcid: 6235069 doi: 10.1182/blood-2018-03-828269
Park, S. M. et al. IKZF2 drives leukemia stem cell self-renewal and inhibits myeloid differentiation. Cell Stem Cell 24, 153–165 e157 (2019).
pubmed: 30472158 doi: 10.1016/j.stem.2018.10.016
Roe, J. S. & Vakoc, C. R. The essential transcriptional function of BRD4 in acute myeloid leukemia. Cold Spring Harb. Symp. Quant. Biol. 81, 61–66 (2016).
pubmed: 28174254 doi: 10.1101/sqb.2016.81.031039
Shi, X. et al. Nuclear NAD(+) homeostasis governed by NMNAT1 prevents apoptosis of acute myeloid leukemia stem cells. Sci. Adv. 7, eabf3895 (2021).
pubmed: 34290089 pmcid: 8294764 doi: 10.1126/sciadv.abf3895
Vegi, N. M. et al. MEIS2 is an oncogenic partner in AML1-ETO-positive AML. Cell Rep. 16, 498–507 (2016).
pubmed: 27346355 doi: 10.1016/j.celrep.2016.05.094
Buenrostro, J. D. et al. Integrated single-cell analysis maps the continuous regulatory landscape of human hematopoietic differentiation. Cell 173, 1535–1548 e1516 (2018).
pubmed: 29706549 pmcid: 5989727 doi: 10.1016/j.cell.2018.03.074
Itoh-Nakadai, A. et al. The transcription repressors Bach2 and Bach1 promote B cell development by repressing the myeloid program. Nat. Immunol. 15, 1171–1180 (2014).
pubmed: 25344725 doi: 10.1038/ni.3024
Iwasaki, H. et al. Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation. Blood 106, 1590–1600 (2005).
pubmed: 15914556 pmcid: 1895212 doi: 10.1182/blood-2005-03-0860
Santaguida, M. et al. JunB protects against myeloid malignancies by limiting hematopoietic stem cell proliferation and differentiation without affecting self-renewal. Cancer Cell 15, 341–352 (2009).
pubmed: 19345332 pmcid: 2669108 doi: 10.1016/j.ccr.2009.02.016
Gaillard, C. et al. Identification of IRF8 as a potent tumor suppressor in murine acute promyelocytic leukemia. Blood Adv. 2, 2462–2466 (2018).
pubmed: 30266821 pmcid: 6177650 doi: 10.1182/bloodadvances.2018018929
Xhabija, B. & Kidder, B. L. KDM5B is a master regulator of the H3K4-methylome in stem cells, development and cancer. Semin. Cancer Biol. 57, 79–85 (2019).
pubmed: 30448242 doi: 10.1016/j.semcancer.2018.11.001
Hinge, A. et al. Asymmetrically segregated mitochondria provide cellular memory of hematopoietic stem cell replicative history and drive HSC attrition. Cell Stem Cell 26, 420–430 e426 (2020).
pubmed: 32059807 pmcid: 7212526 doi: 10.1016/j.stem.2020.01.016
Ho, T. T. et al. Autophagy maintains the metabolism and function of young and old stem cells. Nature 543, 205–210 (2017).
pubmed: 28241143 pmcid: 5344718 doi: 10.1038/nature21388
Spevak, C. C. et al. Hematopoietic stem and progenitor cells exhibit stage-specific translational programs via mTOR- and CDK1-dependent mechanisms. Cell Stem Cell 26, 755–765 e757 (2020).
pubmed: 32386556 pmcid: 9435590 doi: 10.1016/j.stem.2019.12.006
Herrejon Chavez, F. et al. RNA binding protein SYNCRIP maintains proteostasis and self-renewal of hematopoietic stem and progenitor cells. Nat. Commun. 14, 2290 (2023).
pubmed: 37085479 pmcid: 10121618 doi: 10.1038/s41467-023-38001-x
Hidalgo San Jose, L. et al. Modest declines in proteome quality impair hematopoietic stem cell self-renewal. Cell Rep. 30, 69–80 e66 (2020).
pubmed: 31914399 doi: 10.1016/j.celrep.2019.12.003
Liu, J., Valencia-Sanchez, M. A., Hannon, G. J. & Parker, R. MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nat. Cell Biol. 7, 719–723 (2005).
pubmed: 15937477 pmcid: 1855297 doi: 10.1038/ncb1274
Zhao, M., Kim, P., Mitra, R., Zhao, J. & Zhao, Z. TSGene 2.0: an updated literature-based knowledgebase for tumor suppressor genes. Nucleic Acids Res. 44, D1023–D1031 (2016).
pubmed: 26590405 doi: 10.1093/nar/gkv1268
Park, H. J. et al. Therapeutic resistance in acute myeloid leukemia cells is mediated by a novel ATM/mTOR pathway regulating oxidative phosphorylation. eLife 11, e79940 (2022).
pubmed: 36259537 pmcid: 9645811 doi: 10.7554/eLife.79940
Pinto do, O. P., Kolterud, A. & Carlsson, L. Expression of the LIM-homeobox gene LH2 generates immortalized steel factor-dependent multipotent hematopoietic precursors. EMBO J. 17, 5744–5756 (1998).
doi: 10.1093/emboj/17.19.5744
Michlits, G. et al. Multilayered VBC score predicts sgRNAs that efficiently generate loss-of-function alleles. Nat. Methods 17, 708–716 (2020).
pubmed: 32514112 doi: 10.1038/s41592-020-0850-8
Schmoellerl, J. et al. EVI1 drives leukemogenesis through aberrant ERG activation. Blood https://doi.org/10.1182/blood.2022016592 (2022).
de Almeida, M. et al. AKIRIN2 controls the nuclear import of proteasomes in vertebrates. Nature 599, 491–496 (2021).
pubmed: 34711951 doi: 10.1038/s41586-021-04035-8
Maeda, R. et al. RNA decay in processing bodies is indispensable for adipogenesis. Cell Death Dis. 12, 285 (2021).
pubmed: 33731683 pmcid: 7969960 doi: 10.1038/s41419-021-03537-7
Chen, B. et al. Dynamic imaging of genomic loci in living human cells by an optimized CRISPR/Cas system. Cell 155, 1479–1491 (2013).
pubmed: 24360272 pmcid: 3918502 doi: 10.1016/j.cell.2013.12.001
Tsanov, N. et al. smiFISH and FISH-quant - a flexible single RNA detection approach with super-resolution capability. Nucleic Acids Res. 44, e165 (2016).
pubmed: 27599845 pmcid: 5159540 doi: 10.1093/nar/gkw784
Mueller, F. et al. FISH-quant: automatic counting of transcripts in 3D FISH images. Nat. Methods 10, 277–278 (2013).
pubmed: 23538861 doi: 10.1038/nmeth.2406
Buenrostro, J. D., Giresi, P. G., Zaba, L. C., Chang, H. Y. & Greenleaf, W. J. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10, 1213–1218 (2013).
pubmed: 24097267 pmcid: 3959825 doi: 10.1038/nmeth.2688
Blue, S. M. et al. Transcriptome-wide identification of RNA-binding protein binding sites using seCLIP-seq. Nat. Protoc. 17, 1223–1265 (2022).
pubmed: 35322209 pmcid: 11134598 doi: 10.1038/s41596-022-00680-z
Conway, A. E. et al. Enhanced CLIP uncovers IMP protein-RNA targets in human pluripotent stem cells important for cell adhesion and survival. Cell Rep. 15, 666–679 (2016).
pubmed: 27068461 pmcid: 4839292 doi: 10.1016/j.celrep.2016.03.052
Tomas-Daza, L. et al. Low input capture Hi-C (liCHi-C) identifies promoter-enhancer interactions at high-resolution. Nat. Commun. 14, 268 (2023).
pubmed: 36650138 pmcid: 9845235 doi: 10.1038/s41467-023-35911-8
Di Tommaso, P. et al. Nextflow enables reproducible computational workflows. Nat. Biotechnol. 35, 316–319 (2017).
pubmed: 28398311 doi: 10.1038/nbt.3820
Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).
pubmed: 22388286 pmcid: 3322381 doi: 10.1038/nmeth.1923
Liao, Y., Smyth, G. K. & Shi, W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30, 923–930 (2014).
pubmed: 24227677 doi: 10.1093/bioinformatics/btt656
Li, W. et al. MAGeCK enables robust identification of essential genes from genome-scale CRISPR/Cas9 knockout screens. Genome Biol. 15, 554 (2014).
pubmed: 25476604 pmcid: 4290824 doi: 10.1186/s13059-014-0554-4
Wang, B. et al. Integrative analysis of pooled CRISPR genetic screens using MAGeCKFlute. Nat. Protoc. 14, 756–780 (2019).
pubmed: 30710114 pmcid: 6862721 doi: 10.1038/s41596-018-0113-7
Zhang, Y. et al. Model-based analysis of ChIP-seq (MACS). Genome Biol. 9, R137 (2008).
pubmed: 18798982 pmcid: 2592715 doi: 10.1186/gb-2008-9-9-r137
Li, Q. & Zhang, F. A regression framework for assessing covariate effects on the reproducibility of high-throughput experiments. Biometrics 74, 803–813 (2018).
pubmed: 29192968 doi: 10.1111/biom.12832
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
pubmed: 25516281 pmcid: 4302049 doi: 10.1186/s13059-014-0550-8
Yu, G., Wang, L. G. & He, Q. Y. ChIPseeker: an R/Bioconductor package for ChIP peak annotation, comparison and visualization. Bioinformatics 31, 2382–2383 (2015).
pubmed: 25765347 doi: 10.1093/bioinformatics/btv145
Nystrom, S. L. & McKay, D. J. Memes: a motif analysis environment in R using tools from the MEME Suite. PLoS Comput. Biol. 17, e1008991 (2021).
pubmed: 34570758 pmcid: 8496816 doi: 10.1371/journal.pcbi.1008991
Castro-Mondragon, J. A. et al. JASPAR 2022: the 9th release of the open-access database of transcription factor binding profiles. Nucleic Acids Res. 50, D165–D173 (2022).
pubmed: 34850907 doi: 10.1093/nar/gkab1113
Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 25, 1754–1760 (2009).
pubmed: 19451168 pmcid: 2705234 doi: 10.1093/bioinformatics/btp324
Ramirez, F., Dundar, F., Diehl, S., Gruning, B. A. & Manke, T. deepTools: a flexible platform for exploring deep-sequencing data. Nucleic Acids Res. 42, W187–W191 (2014).
pubmed: 24799436 pmcid: 4086134 doi: 10.1093/nar/gku365
Robinson, J. T. et al. Integrative genomics viewer. Nat. Biotechnol. 29, 24–26 (2011).
pubmed: 21221095 pmcid: 3346182 doi: 10.1038/nbt.1754
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).
pubmed: 23104886 doi: 10.1093/bioinformatics/bts635
Tarasov, A., Vilella, A. J., Cuppen, E., Nijman, I. J. & Prins, P. Sambamba: fast processing of NGS alignment formats. Bioinformatics 31, 2032–2034 (2015).
pubmed: 25697820 pmcid: 4765878 doi: 10.1093/bioinformatics/btv098
Xie, Z. et al. Gene set knowledge discovery with Enrichr. Curr. Protoc. 1, e90 (2021).
pubmed: 33780170 pmcid: 8152575 doi: 10.1002/cpz1.90
Huber, W. et al. Orchestrating high-throughput genomic analysis with Bioconductor. Nat. Methods 12, 115–121 (2015).
pubmed: 25633503 pmcid: 4509590 doi: 10.1038/nmeth.3252
Lawrence, M. et al. Software for computing and annotating genomic ranges. PLoS Comput. Biol. 9, e1003118 (2013).
pubmed: 23950696 pmcid: 3738458 doi: 10.1371/journal.pcbi.1003118
Shishkova, E., Hebert, A. S., Westphall, M. S. & Coon, J. J. Ultra-high pressure (>30,000 psi) packing of capillary columns enhancing depth of shotgun proteomic analyses. Anal. Chem. 90, 11503–11508 (2018).
pubmed: 30179449 pmcid: 6478162 doi: 10.1021/acs.analchem.8b02766
Cox, J. & Mann, M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat. Biotechnol. 26, 1367–1372 (2008).
pubmed: 19029910 doi: 10.1038/nbt.1511
Brademan, D. R. et al. Argonaut: a web platform for collaborative multi-omic data visualization and exploration. Patterns 1, 100122 (2020).
pubmed: 33154995 pmcid: 7641515 doi: 10.1016/j.patter.2020.100122
Xiao, Z., Zou, Q., Liu, Y. & Yang, X. Genome-wide assessment of differential translations with ribosome profiling data. Nat. Commun. 7, 11194 (2016).
pubmed: 27041671 pmcid: 4822032 doi: 10.1038/ncomms11194

Auteurs

Srikanth Kodali (S)

Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA.
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Ludovica Proietti (L)

Institute for Medical Biochemistry, University of Veterinary Medicine Vienna, Vienna, Austria.

Gemma Valcarcel (G)

Josep Carreras Leukaemia Research Institute, Badalona, Spain.

Anna V López-Rubio (AV)

Josep Carreras Leukaemia Research Institute, Badalona, Spain.

Patrizia Pessina (P)

Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA.
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Thomas Eder (T)

Institute for Medical Biochemistry, University of Veterinary Medicine Vienna, Vienna, Austria.

Junchao Shi (J)

Division of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, CA, USA.

Annie Jen (A)

Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI, USA.

Núria Lupión-Garcia (N)

Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA.
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Anne C Starner (AC)

Verna & Marrs McLean Department of Biochemistry & Molecular Biology and Therapeutic Innovation Center, Baylor College of Medicine, Houston, TX, USA.

Mason D Bartels (MD)

Verna & Marrs McLean Department of Biochemistry & Molecular Biology and Therapeutic Innovation Center, Baylor College of Medicine, Houston, TX, USA.

Yingzhi Cui (Y)

Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA.
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Caroline M Sands (CM)

Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA.
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Ainoa Planas-Riverola (A)

Josep Carreras Leukaemia Research Institute, Badalona, Spain.

Alba Martínez (A)

Josep Carreras Leukaemia Research Institute, Badalona, Spain.

Talia Velasco-Hernandez (T)

Josep Carreras Leukaemia Research Institute, Badalona, Spain.

Laureano Tomás-Daza (L)

Josep Carreras Leukaemia Research Institute, Badalona, Spain.

Bernhard Alber (B)

Institute for Medical Biochemistry, University of Veterinary Medicine Vienna, Vienna, Austria.

Gabriele Manhart (G)

Institute for Medical Biochemistry, University of Veterinary Medicine Vienna, Vienna, Austria.

Isabella Maria Mayer (IM)

Institute of Pharmacology and Toxicology, University of Veterinary Medicine Vienna, Vienna, Austria.

Karoline Kollmann (K)

Institute of Pharmacology and Toxicology, University of Veterinary Medicine Vienna, Vienna, Austria.

Alessandro Fatica (A)

Department of Biology and Biotechnology 'Charles Darwin', Sapienza University of Rome, Rome, Italy.

Pablo Menendez (P)

Josep Carreras Leukaemia Research Institute, Badalona, Spain.

Evgenia Shishkova (E)

Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI, USA.
National Center for Quantitative Biology of Complex Systems, Madison, WI, USA.

Rachel E Rau (RE)

Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA.
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA.

Biola M Javierre (BM)

Josep Carreras Leukaemia Research Institute, Badalona, Spain.

Joshua Coon (J)

Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI, USA.
National Center for Quantitative Biology of Complex Systems, Madison, WI, USA.
Department of Chemistry, University of Wisconsin, Madison, WI, USA.
Morgridge Institute for Research, Madison, WI, USA.

Qi Chen (Q)

Molecular Medicine Program, Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT, USA.

Eric L Van Nostrand (EL)

Verna & Marrs McLean Department of Biochemistry & Molecular Biology and Therapeutic Innovation Center, Baylor College of Medicine, Houston, TX, USA.

Jose L Sardina (JL)

Josep Carreras Leukaemia Research Institute, Badalona, Spain. jsardina@carrerasresearch.org.

Florian Grebien (F)

Institute for Medical Biochemistry, University of Veterinary Medicine Vienna, Vienna, Austria. Florian.Grebien@vetmeduni.ac.at.
St. Anna Children's Cancer Research Institute (CCRI), Vienna, Austria. Florian.Grebien@vetmeduni.ac.at.
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria. Florian.Grebien@vetmeduni.ac.at.

Bruno Di Stefano (B)

Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA. bruno.distefano@bcm.edu.
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA. bruno.distefano@bcm.edu.
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA. bruno.distefano@bcm.edu.
Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA. bruno.distefano@bcm.edu.
Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. bruno.distefano@bcm.edu.

Classifications MeSH