AI Article Synopsis
- The study investigates RNA splicing fidelity and highlights the role of various proteins, including TDP-43, PTBP1, and PTBP2, in repressing nonconserved cryptic exons.
- While TDP-43 uses UG microsatellites for repression, PTBP1 and PTBP2 use CU microsatellites to target both conserved tissue-specific and nonconserved cryptic exons.
- The findings suggest that PTBP1 and PTBP2 are part of a larger family of splicing factors that help regulate transcript diversity necessary for neuronal differentiation.
Article Abstract
The fidelity of RNA splicing is maintained by a network of factors, but the molecular mechanisms that govern this process have yet to be fully elucidated. We previously found that TDP-43, an RNA-binding protein implicated in neurodegenerative disease, utilizes UG microsatellites to repress nonconserved cryptic exons and prevent their incorporation into mRNA. Here, we report that two well-characterized splicing factors, polypyrimidine tract-binding protein 1 (PTBP1) and polypyrimidine tract-binding protein 2 (PTBP2), are also nonconserved cryptic exon repressors. In contrast to TDP-43, PTBP1 and PTBP2 utilize CU microsatellites to repress both conserved tissue-specific exons and nonconserved cryptic exons. Analysis of these conserved splicing events suggests that PTBP1 and PTBP2 repression is titrated to generate the transcriptome diversity required for neuronal differentiation. We establish that PTBP1 and PTBP2 are members of a family of cryptic exon repressors.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5082185 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2016.08.071 | DOI Listing |
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