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Living or dying by RNA processing: caspase expression in NSCLC
Ganesh Shankarling, Kristen W. Lynch
Ganesh Shankarling, Kristen W. Lynch
Published October 25, 2010
Citation Information: J Clin Invest. 2010;120(11):3798-3801. https://doi.org/10.1172/JCI45037.
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Commentary

Living or dying by RNA processing: caspase expression in NSCLC

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Abstract

Protein expression in humans is controlled by numerous RNA processing steps that occur between transcription of a gene and translation of protein. However, the importance of such regulatory steps to human diseases, especially cancer, is just now coming to light. Changes in the alternative splicing or stability of mRNA transcribed from genes involved in cell-cycle control, cell proliferation, and apoptosis has been linked to tumor formation and progression. Nevertheless, in the majority of these cases, the identity of the regulators that control the expression of such cancer-related genes is poorly understood. In this issue of the JCI, Goehe et al. demonstrate that heterogeneous nuclear ribonuclear protein family member L (hnRNP L), a member of the hnRNP family of RNA processing factors, is specifically phosphorylated in non–small cell lung cancer (NSCLC). The phosphorylated hnRNP L, in turn, promotes expression of the antiapoptotic form of caspase-9, thereby contributing to tumorigenesis.

Authors

Ganesh Shankarling, Kristen W. Lynch

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Figure 1

The processing of a nascent transcript involves numerous potential points of regulation.

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The processing of a nascent transcript involves numerous potential point...
Pre-mRNA molecules synthesized in the nucleus are subjected to specific RNA processing steps in both the nucleus and cytosol of cells. The RNA processing events in the nucleus include capping, splicing, and 3′-end processing (and, in some cases, RNA editing), while regulation of poly(A) tail length typically occurs in the cytosol. Each of these RNA processing steps can be regulated so as to generate multiple mRNA isoforms of a given gene. The depicted pre-mRNA molecule (boxes represent exons, while the line denotes introns) can be differentially spliced to generate mRNA isoforms that encode functionally distinct proteins. Pre-mRNA alternative splicing can also dictate isoform expression by regulating mRNA stability via inducing/blocking NMD. Differential isoform expression can further be achieved by regulating the mRNA export of specific isoforms. In the cytosol, mRNAs containing degradation signals can be selectively degraded, in turn leading to differential protein isoform expression. In each of the above scenarios, regulation is brought about by recognition of cis-acting elements in the pre-mRNA/mRNA by cognate trans-acting factors that promote (green ovals) or inhibit (red ovals) particular events. Light gray boxes indicate mRNAs subject to degradation. "AAAn" refers to the addition of a poly(A) tail.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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