Reciprocal regulation of hnRNP C and CELF2 through translation and transcription tunes splicing activity in T cells
| Autor: | Matthew R. Gazzara, Rakesh Chatrikhi, Robert Jordan Ontiveros, Michael J. Mallory, Kristen W. Lynch, Sean P. McClory |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Transcription
Genetic AcademicSubjects/SCI00010 RNA Splicing T-Lymphocytes Gene regulatory network RNA-binding protein Nerve Tissue Proteins Biology Heterogeneous ribonucleoprotein particle Transcriptome 03 medical and health sciences Jurkat Cells 0302 clinical medicine Transcription (biology) Gene expression Genetics RNA and RNA-protein complexes CELF Proteins Humans 030304 developmental biology Regulation of gene expression 0303 health sciences Heterogeneous-Nuclear Ribonucleoprotein Group C Cell biology Gene Expression Regulation Protein Biosynthesis RNA splicing 030217 neurology & neurosurgery |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | RNA binding proteins (RBPs) frequently regulate the expression of other RBPs in mammalian cells. Such cross-regulation has been proposed to be important to control networks of coordinated gene expression; however, much remains to be understood about how such networks of cross-regulation are established and what the functional consequence is of coordinated or reciprocal expression of RBPs. Here we demonstrate that the RBPs CELF2 and hnRNP C regulate the expression of each other, such that depletion of one results in reduced expression of the other. Specifically, we show that loss of hnRNP C reduces the transcription of CELF2 mRNA, while loss of CELF2 results in decreased efficiency of hnRNP C translation. We further demonstrate that this reciprocal regulation serves to fine tune the splicing patterns of many downstream target genes. Together, this work reveals new activities of hnRNP C and CELF2, provides insight into a previously unrecognized gene regulatory network, and demonstrates how cross-regulation of RBPs functions to shape the cellular transcriptome. |
| Databáze: | OpenAIRE |
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