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Functional analyses of human LUC7-like proteins involved in splicing regulation and myeloid neoplasms.
- Source :
-
Cell reports [Cell Rep] 2021 Apr 13; Vol. 35 (2), pp. 108989. - Publication Year :
- 2021
-
Abstract
- 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.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Base Sequence
Exons
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Introns
Leukemia, Myeloid metabolism
Leukemia, Myeloid pathology
Mutation
Myelodysplastic Syndromes metabolism
Myelodysplastic Syndromes pathology
Nuclear Proteins metabolism
RNA, Small Nuclear genetics
RNA, Small Nuclear metabolism
RNA-Binding Proteins metabolism
Ribonucleoprotein, U1 Small Nuclear genetics
Ribonucleoprotein, U1 Small Nuclear metabolism
Saccharomyces cerevisiae genetics
Saccharomyces cerevisiae metabolism
Saccharomyces cerevisiae Proteins genetics
Saccharomyces cerevisiae Proteins metabolism
Signal Transduction
Spliceosomes
Leukemia, Myeloid genetics
Myelodysplastic Syndromes genetics
Nuclear Proteins genetics
RNA Splicing
RNA-Binding Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 35
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 33852859
- Full Text :
- https://doi.org/10.1016/j.celrep.2021.108989