Functional analyses of human LUC7-like proteins involved in splicing regulation and myeloid neoplasms.
Base Sequence
Exons
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Introns
Leukemia, Myeloid
/ genetics
Mutation
Myelodysplastic Syndromes
/ genetics
Nuclear Proteins
/ genetics
RNA Splicing
RNA, Small Nuclear
/ genetics
RNA-Binding Proteins
/ genetics
Ribonucleoprotein, U1 Small Nuclear
/ genetics
Saccharomyces cerevisiae
/ genetics
Saccharomyces cerevisiae Proteins
/ genetics
Signal Transduction
Spliceosomes
5′ splice site
LUC7L
LUC7L2
LUC7L3
alternative splicing
myeloid neoplasms
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
13 04 2021
13 04 2021
Historique:
received:
09
11
2020
revised:
12
02
2021
accepted:
23
03
2021
entrez:
14
4
2021
pubmed:
15
4
2021
medline:
15
2
2022
Statut:
ppublish
Résumé
Vertebrates have evolved three paralogs, termed LUC7L, LUC7L2, and LUC7L3, of the essential yeast U1 small nuclear RNA (snRNA)-associated splicing factor Luc7p. We investigated the mechanistic and regulatory functions of these putative splicing factors, of which one (LUC7L2) is mutated or deleted in myeloid neoplasms. Protein interaction data show that all three proteins bind similar core but distinct regulatory splicing factors, probably mediated through their divergent arginine-serine-rich domains, which are not present in Luc7p. Knockdown of each factor reveals mostly unique sets of significantly dysregulated alternative splicing events dependent on their binding locations, which are largely non-overlapping. Notably, knockdown of LUC7L2 alone significantly upregulates the expression of multiple spliceosomal factors and downregulates glycolysis genes, possibly contributing to disease pathogenesis. RNA binding studies reveal that LUC7L2 and LUC7L3 crosslink to weak 5' splice sites and to the 5' end of U1 snRNA, establishing an evolutionarily conserved role in 5' splice site selection.
Identifiants
pubmed: 33852859
pii: S2211-1247(21)00303-X
doi: 10.1016/j.celrep.2021.108989
pmc: PMC8078730
mid: NIHMS1693706
pii:
doi:
Substances chimiques
LUC7L protein, human
0
LUC7L2 protein, human
0
LUC7L3 protein, human
0
Luc7 protein, S cerevisiae
0
Nuclear Proteins
0
RNA, Small Nuclear
0
RNA-Binding Proteins
0
Ribonucleoprotein, U1 Small Nuclear
0
SNRNP70 protein, human
0
Saccharomyces cerevisiae Proteins
0
U1 small nuclear RNA
0
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
108989Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL132071
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL135795
Pays : United States
Organisme : NHLBI NIH HHS
ID : F31 HL131140
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL146372
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA204373
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA043703
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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