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Multilayered Control of Alternative Splicing Regulatory Networks by Transcription Factors
- Source :
- Molecular cell. 65(3)
- Publication Year :
- 2016
-
Abstract
- Networks of coordinated alternative splicing (AS) events play critical roles in development and disease. However, a comprehensive knowledge of the factors that regulate these networks is lacking. We describe a high-throughput system for systematically linking trans-acting factors to endogenous RNA regulatory events. Using this system, we identify hundreds of factors associated with diverse regulatory layers that positively or negatively control AS events linked to cell fate. Remarkably, more than one-third of the regulators are transcription factors. Further analyses of the zinc finger protein Zfp871 and BTB/POZ domain transcription factor Nacc1, which regulate neural and stem cell AS programs, respectively, reveal roles in controlling the expression of specific splicing regulators. Surprisingly, these proteins also appear to regulate target AS programs via binding RNA. Our results thus uncover a large “missing cache” of splicing regulators among annotated transcription factors, some of which dually regulate AS through direct and indirect mechanisms.
- Subjects :
- 0301 basic medicine
SPAR-seq
Exonic splicing enhancer
RNA polymerase II
Computational biology
neuroblastoma cells
high-throughput screening
Cell Line
03 medical and health sciences
Mice
RNA interference
Animals
Humans
Gene Regulatory Networks
RNA, Messenger
Transcription factor
Molecular Biology
Embryonic Stem Cells
Cis-regulatory module
Genetics
Zinc finger
Neurons
biology
General transcription factor
Sequence Analysis, RNA
Alternative splicing
Cell Biology
Alternative Splicing
030104 developmental biology
HEK293 Cells
splicing factors
RNA splicing
biology.protein
chromatin
spliceosome
alternative splicing
embryonic stem cells
transcription factors
Transcription Factors
Subjects
Details
- ISSN :
- 10974164
- Volume :
- 65
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Molecular cell
- Accession number :
- edsair.doi.dedup.....225901fcacb633d759a80ab3005f7e3f