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Int. J. Mol. Sci. 2015, 16(1), 452-475; doi:10.3390/ijms16010452

Alternative RNA Structure-Coupled Gene Regulations in Tumorigenesis

1
Institute of Population Health Sciences, National Health Research Institutes, Miaoli County 350, Taiwan
2
Department of Biological Science and Technology, National Chiao-Tung University, Hsinchu 300, Taiwan
3
Department of Dentistry, China Medical University, Taichung 404, Taiwan 
Academic Editor: Akila Mayeda
Received: 31 October 2014 / Accepted: 16 December 2014 / Published: 29 December 2014
(This article belongs to the Special Issue Pre-mRNA Splicing)
View Full-Text   |   Download PDF [631 KB, uploaded 29 December 2014]   |  

Abstract

Alternative RNA structures (ARSs), or alternative transcript isoforms, are critical for regulating cellular phenotypes in humans. In addition to generating functionally diverse protein isoforms from a single gene, ARS can alter the sequence contents of 5'/3' untranslated regions (UTRs) and intronic regions, thus also affecting the regulatory effects of these regions. ARS may introduce premature stop codon(s) into a transcript, and render the transcript susceptible to nonsense-mediated decay, which in turn can influence the overall gene expression level. Meanwhile, ARS can regulate the presence/absence of upstream open reading frames and microRNA targeting sites in 5'UTRs and 3'UTRs, respectively, thus affecting translational efficiencies and protein expression levels. Furthermore, since ARS may alter exon-intron structures, it can influence the biogenesis of intronic microRNAs and indirectly affect the expression of the target genes of these microRNAs. The connections between ARS and multiple regulatory mechanisms underline the importance of ARS in determining cell fate. Accumulating evidence indicates that ARS-coupled regulations play important roles in tumorigenesis. Here I will review our current knowledge in this field, and discuss potential future directions. View Full-Text
Keywords: gene regulation; alternative splicing; alternative promoter usage; alternative cleavage and polyadenylation; untranslated region; nonsense-mediated decay; upstream open reading frame; internal ribosome entry site; microRNA; tumorigenesis gene regulation; alternative splicing; alternative promoter usage; alternative cleavage and polyadenylation; untranslated region; nonsense-mediated decay; upstream open reading frame; internal ribosome entry site; microRNA; tumorigenesis
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Chen, F.-C. Alternative RNA Structure-Coupled Gene Regulations in Tumorigenesis. Int. J. Mol. Sci. 2015, 16, 452-475.

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