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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

Two types of regulatory interactions between 5'UTR and 3'UTR. (A) 3'UTR can negatively regulate the translational inhibitory effect of the uORF in the same transcript; (B) By binding to 3'UTR, microRNAs can selectively regulate the activities of IRESs. Note that this illustration does not show the exact transcript structures of the genes (HER-2 or VEGF-A) mentioned in the text.
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ijms-16-00452-f004: Two types of regulatory interactions between 5'UTR and 3'UTR. (A) 3'UTR can negatively regulate the translational inhibitory effect of the uORF in the same transcript; (B) By binding to 3'UTR, microRNAs can selectively regulate the activities of IRESs. Note that this illustration does not show the exact transcript structures of the genes (HER-2 or VEGF-A) mentioned in the text.

Mentions: uORFs have been found in the transcripts of cancer-related genes. For example, the HER-2 (human epidermal growth factor receptor 2) oncogene expresses mRNAs with uORFs, which have been shown to regulate the translation of HER-2 [82]. Unexpectedly, however, the HER-2 mRNA is more efficiently translated in cancer cells than in normal cells despite the presence of uORF in the transcripts in both cell types [83]. This cell type-specific regulation has been reported to rely on 3'UTR, which can counteract the inhibitory effect of uORF in cancer cells [84] (Figure 4A). This is an excellent example of 5'UTR and 3'UTR interacting with each other to regulate gene expression. The prevalence of this 5'–3' interaction remains unclear. Notably, however, the lengths and compositions of both 5' and 3' UTRs can be significantly affected by AS, which positions AS as an upstream regulatory switch.


Alternative RNA structure-coupled gene regulations in tumorigenesis.

Chen FC - Int J Mol Sci (2014)

Two types of regulatory interactions between 5'UTR and 3'UTR. (A) 3'UTR can negatively regulate the translational inhibitory effect of the uORF in the same transcript; (B) By binding to 3'UTR, microRNAs can selectively regulate the activities of IRESs. Note that this illustration does not show the exact transcript structures of the genes (HER-2 or VEGF-A) mentioned in the text.
© Copyright Policy
Related In: Results  -  Collection

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

ijms-16-00452-f004: Two types of regulatory interactions between 5'UTR and 3'UTR. (A) 3'UTR can negatively regulate the translational inhibitory effect of the uORF in the same transcript; (B) By binding to 3'UTR, microRNAs can selectively regulate the activities of IRESs. Note that this illustration does not show the exact transcript structures of the genes (HER-2 or VEGF-A) mentioned in the text.
Mentions: uORFs have been found in the transcripts of cancer-related genes. For example, the HER-2 (human epidermal growth factor receptor 2) oncogene expresses mRNAs with uORFs, which have been shown to regulate the translation of HER-2 [82]. Unexpectedly, however, the HER-2 mRNA is more efficiently translated in cancer cells than in normal cells despite the presence of uORF in the transcripts in both cell types [83]. This cell type-specific regulation has been reported to rely on 3'UTR, which can counteract the inhibitory effect of uORF in cancer cells [84] (Figure 4A). This is an excellent example of 5'UTR and 3'UTR interacting with each other to regulate gene expression. The prevalence of this 5'–3' interaction remains unclear. Notably, however, the lengths and compositions of both 5' and 3' UTRs can be significantly affected by AS, which positions AS as an upstream regulatory switch.

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