YTHDC2 is essential for pachytene progression and prevents aberrant microtubule-driven telomere clustering in male meiosis
| Autor: | Rong Liu, Seth D. Kasowitz, David Homolka, N. Adrian Leu, Jordan T. Shaked, Gordon Ruthel, Devanshi Jain, Huijuan Lin, Scott Keeney, Mengcheng Luo, Ramesh S. Pillai, P. Jeremy Wang |
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| Předmět: |
Male
QH301-705.5 chromatin condensation Microtubules Article General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences checkpoint 0302 clinical medicine Spermatocytes YTHDC2 Animals meiosis Biology (General) 030304 developmental biology Mice Knockout telomere 0303 health sciences 3. Good health Mice Inbred C57BL pachytene Female Pachytene Stage Transcriptome RNA Helicases 030217 neurology & neurosurgery |
| Zdroj: | BASE-Bielefeld Academic Search Engine Cell Reports, Vol 37, Iss 11, Pp 110110-(2021) Cell reports |
| DOI: | 10.1016/j.celrep.2021.110110 |
| Popis: | SUMMARY Mechanisms driving the prolonged meiotic prophase I in mammals are poorly understood. RNA helicase YTHDC2 is critical for mitosis to meiosis transition. However, YTHDC2 is highly expressed in pachytene cells. Here we identify an essential role for YTHDC2 in meiotic progression. Specifically, YTHDC2 deficiency causes microtubule-dependent telomere clustering and apoptosis at the pachytene stage of prophase I. Depletion of YTHDC2 results in a massively dysregulated transcriptome in pachytene cells, with a tendency toward upregulation of genes normally expressed in mitotic germ cells and downregulation of meiotic transcripts. Dysregulation does not correlate with m6A status, and YTHDC2-bound mRNAs are enriched in genes upregulated in mutant germ cells, revealing that YTHDC2 primarily targets mRNAs for degradation. Furthermore, altered transcripts in mutant pachytene cells encode microtubule network proteins. Our results demonstrate that YTHDC2 regulates the pachytene stage by perpetuating a meiotic transcriptome and preventing microtubule network changes that could lead to telomere clustering. In brief Mechanisms driving the prolonged meiotic prophase I in mammals are poorly understood. Liu et al. show that RNA helicase YTHDC2 regulates the pachytene stage of meiotic prophase I by perpetuating a meiotic transcriptome and preventing microtubule network changes that could lead to telomere clustering. Graphical Abstract |
| Databáze: | OpenAIRE |
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