Alternative RNA Structure-Coupled Gene Regulations in Tumorigenesis

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.

LNC473 Regulating APAF1 IRES-Dependent Translation via Competitive Sponging miR574 and miR15b: Implications in Colorectal Cancer

“…Importantly, the 5 0 UTR of APAF1 mRNA is relatively long, G-C rich, and has the potential to fold into IRES, which is effectively active in a range of human cancer cells, including HEK293T, HeLa, human hepatic carcinoma cell HepG2, and breast cancer MCF7 cells. 38 The IRES-mediated translation was maintained at a constant cellular level of APAF1 protein, even under conditions where cap-independent translation was compromised. 20 Currently, in contrast to an improved perception of the mechanism of viral IRES element action, exceedingly little is known about the underlying mechanism and the importance of cellular IRES-mediated translation.…”

Association of BCSC-1 with human esophageal squamous cell carcinoma

“…Little is known about the cellular function and related molecular mechanism of BCSC-1 involved in tumorigenesis. Tumorigenesis is a very complicated process regulated by a number of factors [15][16][17][18][19][20]. TSG has been found to exhibit multiple inhibitive effects on tumorigenesis [21][22][23].…”

Intrinsic Regulatory Role of RNA Structural Arrangement in Alternative Splicing Control

“…The range of deregulated processes in cancer cells make it impossible to emerge early molecular alterations leading the cell to a tumorigenic pathway. AS is one of these processes which is vastly disturbed and contributes to nearly all deleterious cancer cell phenotypes including metastasis, angiogenesis, or proliferation [ 317 , 318 , 319 , 320 , 321 ]. The enrichment of alterations of RNA folding in cancer genomes, whether directly imposed by riboSNitches or indirectly through mutations or alterations in expression of RNA remodelers, was found to be most likely pathogenic and could be accountable for cancer-associated molecular changes including missplicing [ 139 , 140 , 322 ].…”

“…The enrichment of alterations of RNA folding in cancer genomes, whether directly imposed by riboSNitches or indirectly through mutations or alterations in expression of RNA remodelers, was found to be most likely pathogenic and could be accountable for cancer-associated molecular changes including missplicing [ 139 , 140 , 322 ]. The function of RNA structure remodelers and their structure-related effect on cis -regulatory elements are greatly correlated with AS regulation of proto-oncogenes and tumor suppressors [ 318 , 323 ]. Due to the fact that in various cancer types their level is substantially altered, the mechanism and functional relevance of RNA remodelers in pathogenic and invasive phenotype of cancer cells remain under extensive investigation [ 321 , 324 ].…”