AI Article Synopsis
- The role of alternative splicing (AS) in stem cells is not well understood, especially compared to transcriptional regulation.
- Researchers studied AS in planarian stem cells and found a conserved program that includes many different alternative exons and introns, revealing key regulators of this process.
- The interaction between CELF and MBNL proteins is crucial for regulating stem cell-specific AS, and altering these factors affects the stem cells’ ability to regenerate and differentiate.
Article Abstract
In contrast to transcriptional regulation, the function of alternative splicing (AS) in stem cells is poorly understood. In mammals, MBNL proteins negatively regulate an exon program specific of embryonic stem cells; however, little is known about the in vivo significance of this regulation. We studied AS in a powerful in vivo model for stem cell biology, the planarian Schmidtea mediterranea. We discover a conserved AS program comprising hundreds of alternative exons, microexons and introns that is differentially regulated in planarian stem cells, and comprehensively identify its regulators. We show that functional antagonism between CELF and MBNL factors directly controls stem cell-specific AS in planarians, placing the origin of this regulatory mechanism at the base of Bilaterians. Knockdown of CELF or MBNL factors lead to abnormal regenerative capacities by affecting self-renewal and differentiation sets of genes, respectively. These results highlight the importance of AS interactions in stem cell regulation across metazoans.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4978528 | PMC |
| http://dx.doi.org/10.7554/eLife.16797 | DOI Listing |
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