Abstract
Signal transduction pathways transmit the information received from external and internal cues and generate a response that allows the cell to adapt to changes in the surrounding environment. Signaling pathways trigger rapid responses by changing the activity or localization of existing molecules, as well as long-term responses that require the activation of gene expression programs. All steps involved in the regulation of gene expression, from transcription to processing and utilization of new transcripts, are modulated by multiple signal transduction pathways. This review provides a broad overview of the post-translational regulation of factors involved in RNA processing events by signal transduction pathways, with particular focus on the regulation of pre-mRNA splicing, cleavage and polyadenylation. The effects of several post-translational modifications (i.e., sumoylation, ubiquitination, methylation, acetylation and phosphorylation) on the expression, subcellular localization, stability and affinity for RNA and protein partners of many RNA-binding proteins are highlighted. Moreover, examples of how some of the most common signal transduction pathways can modulate biological processes through changes in RNA processing regulation are illustrated. Lastly, we discuss challenges and opportunities of therapeutic approaches that correct RNA processing defects and target signaling molecules.
Highlights
This study identified several other RNA-binding proteins (RBPs) involved in RNA processing that are recruited to sites of DNA lesions, which may be required for the processing of the newly discovered small non-coding RNAs that are an integral part of the DNA damage response (DDR) pathway [197]
Specific stimulus-dependent signaling pathways are activated in the proper time windows to respond to environmental cues
These pathways allow the coordination of the activity of many proteins and RNA molecules that are already present in the cell, as well the induction of the expression of other molecules that are required only under specific conditions
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. One of the main responses of the cell to a change in the surrounding environment is modulation of the expression of genes that encode proteins and RNAs involved in the specific biological processes that need to be activated or repressed. PTM of histones is crucial to determine the accessibility of their chromatin to the transcriptional apparatus and is a main determinant of gene expression regulation in response to signaling pathways activated by external or internal cues [7,8,9]. Two of these processes—the splicing of introns and the cleavage and polyadenylation of the 30 end of the transcript—are extensively modulated by signaling pathways through PTM of the factors involved in these mechanisms. We will briefly describe the main features of the splicing and polyadenylation processes and illustrate selected examples of how signal transduction pathways impinge on their regulation in eukaryotic cells
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