Regulation of gene expression in mammalian nervous system through alternative pre-mRNA splicing coupled with RNA quality control mechanisms.
Eukaryotic gene expression is orchestrated on a genome-wide scale through several post-transcriptional mechanisms. Of these, alternative pre-mRNA splicing expands the proteome diversity and modulates mRNA stability through downstream RNA quality control (QC) pathways including nonsense-mediated decay (NMD) of mRNAs containing premature termination codons and nuclear retention and elimination (NRE) of intron-containing transcripts. Although originally identified as mechanisms for eliminating aberrant transcripts, a growing body of evidence suggests that NMD and NRE coupled with deliberate changes in pre-mRNA splicing patterns are also used in a number of biological contexts for deterministic control of gene expression. Here we review recent studies elucidating molecular mechanisms and biological significance of these gene regulation strategies with a specific focus on their roles in nervous system development and physiology. This article is part of a Special Issue entitled 'RNA and splicing regulation in neurodegeneration'.
School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore.
Karen
K
Yap
Eugene V
EV
Makeyev
D017398:Alternative Splicing; D000818:Animals; D006801:Humans; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D059365:Nonsense Mediated mRNA Decay; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger
Alternative pre-mRNA splicing; Nervous system development and function; Nonsense-mediated decay; Nuclear retention and elimination of incompletely spliced transcripts; Post-transcriptional regulation of gene expression; RNA quality control