Abstract:
:The identification of telomerase-negative HAATI (heterochromatin amplification-mediated and telomerase-independent) cells, in which telomeres are superseded by nontelomeric heterochromatin tracts, challenged the idea that canonical telomeres are essential for chromosome linearity and raised crucial questions as to how such tracts translocate to eroding chromosome ends and confer end protection. Here we show that HAATI arises when telomere loss triggers a newly recognized illegitimate translocation pathway that requires RNAi factors. While RNAi is necessary for the translocation events that mobilize ribosomal DNA (rDNA) tracts to all chromosome ends (forming "HAATIrDNA" chromosomes), it is dispensable for HAATIrDNA maintenance. Surprisingly, Dicer (Dcr1) plays a separate, RNAi-independent role in preventing formation of the rare HAATI subtype in which a different repetitive element (the subtelomeric element) replaces telomeres. Using genetics and fusions between shelterin components and rDNA-binding proteins, we mapped the mechanism by which rDNA loci engage crucial end protection factors-despite the absence of telomere repeats-and secure end protection. Sequence analysis of HAATIrDNA genomes allowed us to propose RNA and DNA polymerase template-switching models for the mechanism of RNAi-triggered rDNA translocations. Collectively, our results reveal unforeseen roles for noncoding RNAs (ncRNAs) in assembling a telomere-free chromosome end protection device.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Begnis M,Apte MS,Masuda H,Jain D,Wheeler DL,Cooper JPdoi
10.1101/gad.311712.118subject
Has Abstractpub_date
2018-04-01 00:00:00pages
537-554issue
7-8eissn
0890-9369issn
1549-5477pii
gad.311712.118journal_volume
32pub_type
杂志文章abstract::Bone morphogenic proteins 2 and 4 (BMP2 and BMP4) inhibit proliferation and induce differentiation of cerebellar granule neuron progenitors (GNPs) and primary GNP-like medulloblastoma (MB) cells. This occurs through rapid proteasome-mediated degradation of Math1 (Atoh1), a transcription factor expressed in proliferati...
journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
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doi:10.1101/gad.1743009
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journal_title:Genes & development
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doi:10.1101/gad.307132.117
更新日期:2018-03-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
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journal_title:Genes & development
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