Abstract
Post-transcriptional modifications to coding and non-coding RNAs are unquestionably a pivotal way in which human mRNA and protein diversity can influence the different phases of a transcript’s life cycle. CELF (CUGBP Elav-like family) proteins are RBPs (RNA-binding proteins) with pleiotropic capabilities in RNA processing. Their responsibilities extend from alternative splicing and transcript editing in the nucleus to mRNA stability, and translation into the cytoplasm. In this way, CELF family members have been connected to global alterations in cancer proliferation and invasion, leading to their identification as potential tumor suppressors or even oncogenes. Notably, genetic variants, alternative splicing, phosphorylation, acetylation, subcellular distribution, competition with other RBPs, and ultimately lncRNAs, miRNAs, and circRNAs all impact CELF regulation. Discoveries have emerged about the control of CELF functions, particularly via noncoding RNAs, and CELF proteins have been identified as competing, antagonizing, and regulating agents of noncoding RNA biogenesis. On the other hand, CELFs are an intriguing example through which to broaden our understanding of the RBP/noncoding RNA regulatory axis. Balancing these complex pathways in cancer is undeniably pivotal and deserves further research. This review outlines some mechanisms of CELF protein regulation and their functional consequences in cancer physiology.
Highlights
RNA-binding proteins (RBPs) orchestrate crucial aspects of RNA biology in many sets of targets
Binding through 30 UTR, CELF2 can inhibit the translation of MCL1 (Apoptosis Regulator, BCL2 Family Member) anti-apoptotic factor [41]. Another example is the circularization of SHMT1 (Serine Hydroxymethyltransferase 1) mRNA and its internal ribosome entry site (IRES)- mediated translation, which is provided with CELF1-hnRNPH
The misregulation of CELF members and their targets in cancer is a good illustration of how RBPs may regulate a variety of pathways while performing various tasks
Summary
RNA-binding proteins (RBPs) orchestrate crucial aspects of RNA biology in many sets of targets. CELF proteins are involved in RNA splicing through binding to the upstream or downstream intron of an alternative exon to mediate exon skipping or inclusion. They are abundant in the 30 UTR of transcripts associating with mRNA decay or translation [7,8]. Non-coding RNAs of various kinds can directly or indirectly target CELF proteins; these RBPs can significantly alter non-coding RNAs in many ways, forming the noncoding RNA/CELFs regulatory axis. CircRNAs can be found broadly in almost all cells and tissues; they are mainly distributed in the cytoplasm and, rarely, in the nucleus They can function as RNA sponges, nucleators of multiprotein complexes, or even transcriptional regulators [9].
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