RRC ID |
56217
|
著者 |
Saldi TK, Gonzales P, Garrido-Lecca A, Dostal V, Roberts CM, Petrucelli L, Link CD.
|
タイトル |
The Caenorhabditis elegans Ortholog of TDP-43 Regulates the Chromatin Localization of the Heterochromatin Protein 1 Homolog HPL-2.
|
ジャーナル |
Mol Cell Biol
|
Abstract |
TDP-1 is the Caenorhabditis elegans ortholog of mammalian TDP-43, which is strongly implicated in the etiology of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). We discovered that deletion of the tdp-1 gene results in enhanced nuclear RNA interference (RNAi). As nuclear RNAi in C. elegans involves chromatin changes moderated by HPL-2, a homolog of heterochromatin protein 1 (HP1), we investigated the interaction of TDP-1 and HPL-2. We found that TDP-1 and HPL-2 interact directly and that loss of TDP-1 dramatically alters the chromatin association of HPL-2. We showed previously that deletion of the tdp-1 gene results in transcriptional alterations and the accumulation of double-stranded RNA (dsRNA). These molecular changes are replicated in an hpl-2 deletion strain, consistent with HPL-2 acting in consort with TDP-1 to modulate these aspects of RNA metabolism. Our observations identify novel mechanisms by which HP1 homologs can be recruited to chromatin and by which nuclear depletion of human TDP-43 may lead to changes in RNA metabolism that are relevant to disease.
|
巻・号 |
38(15)
|
公開日 |
2018-8-1
|
DOI |
10.1128/MCB.00668-17
|
PII |
MCB.00668-17
|
PMID |
29760282
|
PMC |
PMC6048318
|
MeSH |
Alternative Splicing
Animals
Animals, Genetically Modified
Caenorhabditis elegans / genetics*
Caenorhabditis elegans / metabolism*
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism*
Cell Nucleus / metabolism
Chromatin / metabolism
Chromobox Protein Homolog 5
Chromosomal Proteins, Non-Histone / deficiency
Chromosomal Proteins, Non-Histone / genetics
Chromosomal Proteins, Non-Histone / metabolism*
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism
Gene Deletion
Genes, Helminth
Humans
Neurodegenerative Diseases / etiology
Neurodegenerative Diseases / genetics
Neurodegenerative Diseases / metabolism
RNA Interference
RNA, Helminth / genetics
RNA, Helminth / metabolism
RNA-Binding Proteins / genetics
RNA-Binding Proteins / metabolism*
|
IF |
3.735
|
引用数 |
4
|
リソース情報 |
線虫 |
tm1116
tm1489 |