tRNA Fragments Show Intertwining with mRNAs of Specific Repeat Content and Have Links to Disparities.
Journal
Cancer research
ISSN: 1538-7445
Titre abrégé: Cancer Res
Pays: United States
ID NLM: 2984705R
Informations de publication
Date de publication:
15 06 2019
15 06 2019
Historique:
received:
12
03
2019
revised:
08
04
2019
accepted:
08
04
2019
pubmed:
19
4
2019
medline:
12
3
2020
entrez:
19
4
2019
Statut:
ppublish
Résumé
tRNA-derived fragments (tRF) are a class of potent regulatory RNAs. We mined the datasets from The Cancer Genome Atlas (TCGA) representing 32 cancer types with a deterministic and exhaustive pipeline for tRNA fragments. We found that mitochondrial tRNAs contribute disproportionally more tRFs than nuclear tRNAs. Through integrative analyses, we uncovered a multitude of statistically significant and context-dependent associations between the identified tRFs and mRNAs. In many of the 32 cancer types, these associations involve mRNAs from developmental processes, receptor tyrosine kinase signaling, the proteasome, and metabolic pathways that include glycolysis, oxidative phosphorylation, and ATP synthesis. Even though the pathways are common to multiple cancers, the association of specific mRNAs with tRFs depends on and differs from cancer to cancer. The associations between tRFs and mRNAs extend to genomic properties as well; specifically, tRFs are positively correlated with shorter genes that have a higher density in repeats, such as ALUs, MIRs, and ERVLs. Conversely, tRFs are negatively correlated with longer genes that have a lower repeat density, suggesting a possible dichotomy between cell proliferation and differentiation. Analyses of bladder, lung, and kidney cancer data indicate that the tRF-mRNA wiring can also depend on a patient's sex. Sex-dependent associations involve cyclin-dependent kinases in bladder cancer, the MAPK signaling pathway in lung cancer, and purine metabolism in kidney cancer. Taken together, these findings suggest diverse and wide-ranging roles for tRFs and highlight the extensive interconnections of tRFs with key cellular processes and human genomic architecture. SIGNIFICANCE: Across 32 TCGA cancer contexts, nuclear and mitochondrial tRNA fragments exhibit associations with mRNAs that belong to concrete pathways, encode proteins with particular destinations, have a biased repeat content, and are sex dependent.
Identifiants
pubmed: 30996049
pii: 0008-5472.CAN-19-0789
doi: 10.1158/0008-5472.CAN-19-0789
pmc: PMC6571059
mid: NIHMS1527097
doi:
Substances chimiques
RNA, Messenger
0
RNA, Transfer
9014-25-9
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3034-3049Subventions
Organisme : NCI NIH HHS
ID : R21 CA195204
Pays : United States
Informations de copyright
©2019 American Association for Cancer Research.
Références
RNA. 2005 Jun;11(6):849-52
pubmed: 15872185
Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6605-10
pubmed: 16636294
Urol Int. 2008;80(4):431-8
pubmed: 18587256
Nature. 2008 Oct 23;455(7216):1124-8
pubmed: 18806776
Nat Protoc. 2009;4(1):44-57
pubmed: 19131956
Cancer. 2010 Jan 1;116(1):50-6
pubmed: 19877112
PLoS Comput Biol. 2009 Dec;5(12):e1000610
pubmed: 20019790
Genome Res. 2010 Mar;20(3):320-31
pubmed: 20133333
Curr Biol. 2010 Feb 9;20(3):R110-3
pubmed: 20144771
Semin Cancer Biol. 2010 Aug;20(4):200-10
pubmed: 20600922
Expert Rev Respir Med. 2010 Aug;4(4):509-18
pubmed: 20658912
RNA Biol. 2011 Jan-Feb;8(1):158-77
pubmed: 21282978
PLoS One. 2011;6(7):e21800
pubmed: 21789182
Mol Cell. 2011 Aug 19;43(4):613-23
pubmed: 21855800
Genome Biol. 2011 Dec 28;12(12):236
pubmed: 22204421
Endocr Rev. 2012 Feb;33(1):1-47
pubmed: 22240244
Nat Rev Cancer. 2012 Oct;12(10):685-98
pubmed: 23001348
Proc Natl Acad Sci U S A. 2013 Jan 22;110(4):1404-9
pubmed: 23297232
Nat Biotechnol. 2013 Jun;31(6):522-9
pubmed: 23604282
Nucleic Acids Res. 2013 Aug;41(14):6857-69
pubmed: 23703216
Nature. 2013 Jul 4;499(7456):43-9
pubmed: 23792563
Nat Neurosci. 2014 May;17(5):667-9
pubmed: 24728267
Genome Res. 2014 Jul;24(7):1053-63
pubmed: 24823667
Protein Cell. 2014;5(8):592-602
pubmed: 25015087
Nature. 2014 Jul 31;511(7511):543-50
pubmed: 25079552
Cell. 2014 Sep 11;158(6):1281-1292
pubmed: 25215487
BMC Biol. 2014 Oct 01;12:78
pubmed: 25270025
Bioessays. 2015 Feb;37(2):148-54
pubmed: 25400101
Sci Rep. 2015 Jan 08;5:7675
pubmed: 25567797
RNA Biol. 2015;12(4):375-80
pubmed: 25849196
Cell. 2015 May 7;161(4):790-802
pubmed: 25957686
Proc Natl Acad Sci U S A. 2015 Jul 21;112(29):E3816-25
pubmed: 26124144
Nat Methods. 2015 Sep;12(9):879-84
pubmed: 26237225
Nucleic Acids Res. 2016 Jan 8;44(1):e3
pubmed: 26271990
Oncotarget. 2015 Sep 22;6(28):24797-822
pubmed: 26325506
Gene Regul Syst Bio. 2015 Sep 10;9:27-33
pubmed: 26401098
Cancer Res. 2015 Oct 15;75(20):4429-36
pubmed: 26471915
Life (Basel). 2015 Nov 27;5(4):1638-51
pubmed: 26703738
Science. 2016 Jan 22;351(6271):397-400
pubmed: 26721680
Science. 2016 Jan 22;351(6271):391-396
pubmed: 26721685
Nat Protoc. 2016 Mar;11(3):476-89
pubmed: 26866791
Elife. 2016 Feb 22;5:null
pubmed: 26901439
Bioinformatics. 2016 Aug 15;32(16):2481-9
pubmed: 27153631
Cancer Cell. 2016 May 9;29(5):711-722
pubmed: 27165743
Urol Int. 2016;97(4):373-379
pubmed: 27595416
RNA Biol. 2017 Oct 3;14(10):1364-1373
pubmed: 27892771
Nucleic Acids Res. 2017 Jan 4;45(D1):D158-D169
pubmed: 27899622
J Proteome Res. 2017 Feb 3;16(2):413-420
pubmed: 27936807
Mob DNA. 2016 Dec 1;7:24
pubmed: 27980689
Nucleic Acids Res. 2017 May 19;45(9):e70
pubmed: 28108659
Bioinformatics. 2017 Jul 1;33(13):2034-2036
pubmed: 28203700
Nucleic Acids Res. 2017 Apr 7;45(6):2973-2985
pubmed: 28206648
Sci Rep. 2017 Feb 21;7:41184
pubmed: 28220888
Nucleic Acids Res. 2017 May 19;45(9):5142-5152
pubmed: 28335016
Genome Biol. 2017 May 24;18(1):98
pubmed: 28535802
Nucleic Acids Res. 2017 Sep 6;45(15):9108-9120
pubmed: 28645172
Cell. 2017 Jun 29;170(1):61-71.e11
pubmed: 28666125
BMC Genomics. 2017 Jun 30;18(1):502
pubmed: 28666407
PLoS One. 2017 Oct 12;12(10):e0186039
pubmed: 29023571
Nat Commun. 2017 Oct 13;8(1):918
pubmed: 29030639
Methods Mol Biol. 2018;1680:237-255
pubmed: 29030853
Nucleic Acids Res. 2018 Jan 4;46(D1):D303-D307
pubmed: 29106616
Nucleic Acids Res. 2018 Jan 4;46(D1):D152-D159
pubmed: 29186503
Cancer Res. 2018 Mar 1;78(5):1140-1154
pubmed: 29229607
Sci Rep. 2018 Mar 28;8(1):5314
pubmed: 29593348
PLoS Biol. 2018 Apr 18;16(4):e2005707
pubmed: 29668680
RNA. 2018 Aug;24(8):1093-1105
pubmed: 29844106
Cancer Res. 2018 Oct 1;78(19):5538-5547
pubmed: 30275053