Open AccessReciprocal regulation of hnRNP C and CELF2 through translation and transcription tunes splicing activity in T cells
Author(s) -
Michael J. Mallory,
Sean P. McClory,
Rakesh Chatrikhi,
Matthew R. Gazzara,
Robert Jordan Ontiveros,
Kristen W. Lynch
Publication year - 2020
Publication title -
nucleic acids research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.008
H-Index - 537
eISSN - 1362-4954
pISSN - 0305-1048
DOI - 10.1093/nar/gkaa295
Subject(s) - biology , rna splicing , rna binding protein , translation (biology) , regulation of gene expression , gene expression , transcription (linguistics) , microbiology and biotechnology , translational regulation , gene , genetics , alternative splicing , messenger rna , transcription factor , rna , linguistics , philosophy
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.