E-resources
-
Gable, Dustin L; Gaysinskaya, Valeriya; Atik, Christine C; Talbot, Jr, C Conover; Kang, Byunghak; Stanley, Susan E; Pugh, Elizabeth W; Amat-Codina, Nuria; Schenk, Kara M; Arcasoy, Murat O; Brayton, Cory; Florea, Liliana; Armanios, Mary
Genes & development, 10/2019, Volume: 33, Issue: 19-20Journal Article
Short telomere syndromes manifest as familial idiopathic pulmonary fibrosis; they are the most common premature aging disorders. We used genome-wide linkage to identify heterozygous loss of function of , a zinc-knuckle containing protein, as a cause of autosomal dominant pulmonary fibrosis. ZCCHC8 associated with and was required for telomerase function. In ZCCHC8 knockout cells and in mutation carriers, genomically extended telomerase RNA ( ) accumulated at the expense of mature , consistent with a role for ZCCHC8 in mediating 3' end targeting to the nuclear RNA exosome. We generated -null mice and found that heterozygotes, similar to human mutation carriers, had insufficiency but an otherwise preserved transcriptome. In contrast, mice developed progressive and fatal neurodevelopmental pathology with features of a ciliopathy. The brain transcriptome was highly dysregulated, showing accumulation and 3' end misprocessing of other low-abundance RNAs, including those encoding cilia components as well as the intronless replication-dependent histones. Our data identify a novel cause of human short telomere syndromes-familial pulmonary fibrosis and uncover nuclear exosome targeting as an essential 3' end maturation mechanism that vertebrate shares with replication-dependent histones.
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|
Source: Personal bibliographies
and: SICRIS
The material is available in full text. If you wish to order the material anyway, click the Continue button.