Functions and Mechanisms of mTORC1-Mediated Post-Transcriptional Regulations

Abstract

Post-transcriptional regulations of mRNA transcripts such as alternative splicing and alternative polyadenylation can affect the expression of genes without changing the transcript levels. These events have significant physiological impacts on various biological systems. Nevertheless, how cellular signaling pathways control these post-transcriptional processes in cells has not been very well explored. The mammalian target of rapamycin complex 1 (mTORC1) pathway plays a key role in sensing cellular nutrient and energy status and regulating the proliferation and growth of cells. Dysregulation of mTORC1 pathway is associated with a number of pathological conditions, including cancers. It has been well-known that mTORC1 controls its downstream pathways through translational and/or transcriptional regulation of the expression of key downstream effectors. Yet recent studies have also suggested that mTORC1 can control downstream pathways via post-transcriptional regulations. In this work, I discuss the roles of post-transcriptional processes in gene expression regulations and argue that post-transcriptional regulation is an additional layer of gene expression control by mTORC1 to steer cellular biology. Particularly, I demonstrate this by showing how mTORC1 promotes the transcriptome-wide 3’-UTR shortening, as well as how it controls the expression profile of the functionally distinct isoforms of the splicing factor gene U2AF1 in cells via alternative splicing to modulate the proteome. These emphasize the importance of studying post-transcriptional events in transcriptome datasets for gaining a fuller understanding of gene expression regulations in the biological systems of interest.