Regulatory roles and mechanisms of alternative RNA splicing in adipogenesis and human metabolic health

Abstract

Alternative splicing (AS) regulates gene expression patterns at the post-transcriptional level and generates a striking expansion of coding capacities of genomes and cellular protein diversity. RNA splicing could undergo modulation and close interaction with genetic and epigenetic machinery. Notably, during the adipogenesis processes of white, brown and beige adipocytes, AS tightly interplays with the differentiation gene program networks. Here, we integrate the available findings on specific splicing events and distinct functions of different splicing regulators as examples to highlight the directive biological contribution of AS mechanism in adipogenesis and adipocyte biology. Furthermore, accumulating evidence has suggested that mutations and/or altered expression in splicing regulators and aberrant splicing alterations in the obesity-associated genes are often linked to humans’ diet-induced obesity and metabolic dysregulation phenotypes. Therefore, significant attempts have been finally made to overview novel detailed discussion on the prospects of splicing machinery with obesity and metabolic disorders to supply featured potential management mechanisms in clinical applicability for obesity treatment strategies.

Severe choline deficiency induces alternative splicing aberrance in optimized duck primary hepatocyte cultures

“…Indeed, SE are more prone to creating and changing the protein function due to the deletion of functional motif [ 51 , 52 ]. Moreover, accumulating evidence has suggested that mutations and/or altered expression in splicing regulators and aberrant splicing alterations in the obesity-associated genes are often linked to humans’ diet-induced obesity and metabolic dysregulation phenotypes [ 53 ]. It is well known that choline was involved in regulating the host’s lipid metabolism.…”

Regulatory mechanisms of the early phase of white adipocyte differentiation: an overview

“…Specifically, if PPARγ-1 activity is still poorly understood, PPARγ-2 has been demonstrated to be required for white adipogenesis [ 42 ]. This information is of great relevance since it indicates that mRNA splicing events are necessary to determine the fate of adipocyte precursor cells [ 43 , 44 ]. However, mRNA splicing is only one of many cellular processes that have recently been shown to be critical in the early stages of adipogenesis.…”

Interplays of different types of epitranscriptomic mRNA modifications

“…FTO is particularly interesting as it has the potential to regulate pre-mRNA splicing by altering the m 6 A pattern on pre-mRNAs as well as affecting the spliceosome via targeting m 6 A m and m 6 A in snRNAs [ 82 , 90 , 92 , 93 , 94 ]. Reduction of FTO leads to elevation of m 6 A, which promotes inclusion of dependent on SRSF2 (acting as an m 6 A reader) [ 95 ]. Similarly, to FTO, METTL16 revealed prevalently intronic binding in pre-mRNAs and its depletion led to an altered splicing pattern [ 96 ].…”