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Alternative RNA structure-coupled gene regulations in tumorigenesis.

Chen FC - Int J Mol Sci (2014)

Bottom Line: 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.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 Article: PubMed Central - PubMed

Affiliation: Institute of Population Health Sciences, National Health Research Institutes, Miaoli County 350, Taiwan. fcchen@nrhi.org.tw.

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.

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Related in: MedlinePlus

Connections between AS and the biogenesis of intronic microRNAs. (A) microRNA processors interact with the splicing machinery and participate in RNA splicing; (B) Splicing can disrupt the biogenesis of microRNAs that are located at the exon-intron boundaries; (C) Splicing can serve to delineate microRNAs that are clustered in an intron.
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ijms-16-00452-f005: Connections between AS and the biogenesis of intronic microRNAs. (A) microRNA processors interact with the splicing machinery and participate in RNA splicing; (B) Splicing can disrupt the biogenesis of microRNAs that are located at the exon-intron boundaries; (C) Splicing can serve to delineate microRNAs that are clustered in an intron.

Mentions: MicroRNAs have been demonstrated to contribute significantly to the tumorigenesis of multiple types of cancer [110,111]. These noncoding RNAs are generated from pre-microRNAs by a specific RNA processing machinery that includes Drosha, DGCR8 (DGCR8 microprocessor complex subunit), and other accessory proteins [112]. Most of the pre-microRNAs reside in intergenic regions [113]. Interestingly, however, hundreds of microRNAs have been found to derive from the intronic regions of coding genes [114,115]. The maturation of these intronic microRNAs has been suggested to depend mainly on the splicing machinery instead of the commonly used Drosha/DGCR8 complex [116,117,118,119]. This genic source of microRNA implies correlations between AS and microRNA-mediated gene regulations. Of note, in the case of AS, intronic and exonic regions are interchangeable. The intronic regions that harbor pre-microRNAs may be spliced into coding sequences, thus preventing the biogenesis of these microRNAs. However, this hypothetical AS-microRNA association awaits experimental clarifications (Figure 5).


Alternative RNA structure-coupled gene regulations in tumorigenesis.

Chen FC - Int J Mol Sci (2014)

Connections between AS and the biogenesis of intronic microRNAs. (A) microRNA processors interact with the splicing machinery and participate in RNA splicing; (B) Splicing can disrupt the biogenesis of microRNAs that are located at the exon-intron boundaries; (C) Splicing can serve to delineate microRNAs that are clustered in an intron.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307256&req=5

ijms-16-00452-f005: Connections between AS and the biogenesis of intronic microRNAs. (A) microRNA processors interact with the splicing machinery and participate in RNA splicing; (B) Splicing can disrupt the biogenesis of microRNAs that are located at the exon-intron boundaries; (C) Splicing can serve to delineate microRNAs that are clustered in an intron.
Mentions: MicroRNAs have been demonstrated to contribute significantly to the tumorigenesis of multiple types of cancer [110,111]. These noncoding RNAs are generated from pre-microRNAs by a specific RNA processing machinery that includes Drosha, DGCR8 (DGCR8 microprocessor complex subunit), and other accessory proteins [112]. Most of the pre-microRNAs reside in intergenic regions [113]. Interestingly, however, hundreds of microRNAs have been found to derive from the intronic regions of coding genes [114,115]. The maturation of these intronic microRNAs has been suggested to depend mainly on the splicing machinery instead of the commonly used Drosha/DGCR8 complex [116,117,118,119]. This genic source of microRNA implies correlations between AS and microRNA-mediated gene regulations. Of note, in the case of AS, intronic and exonic regions are interchangeable. The intronic regions that harbor pre-microRNAs may be spliced into coding sequences, thus preventing the biogenesis of these microRNAs. However, this hypothetical AS-microRNA association awaits experimental clarifications (Figure 5).

Bottom Line: 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.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 Article: PubMed Central - PubMed

Affiliation: Institute of Population Health Sciences, National Health Research Institutes, Miaoli County 350, Taiwan. fcchen@nrhi.org.tw.

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.

Show MeSH
Related in: MedlinePlus