|
| Status |
Public on Aug 08, 2014 |
| Title |
human 3' RACE |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Mpn1 proteins are evolutionarily conserved exonucleases that modify spliceosomal U6 small nuclear RNAs (snRNAs) post-transcriptionally. Mutations in the human MPN1 gene are associated to the genodermatosis Clericuzio-type poikiloderma with neutropenia (PN). Mpn1 deficiency leads to aberrant U6 3’ end processing and accelerated U6 decay through unknown molecular mechanisms. Here we show that in mpn1Δ fission yeast cells U6 is barely bound by the protective Lsm2-8 complex, undergoes extensive oligoadenylation and is degraded by the nuclear RNA exonuclease Rrp6 independently of the poly(A) polymerase Cid14/Trf4. Mpn1 processes U6 in a spliceosome-dependent manner, as mutant U6 molecules that fail to join the spliceosome are not substrates for Mpn1. Moreover, human U6atac, the U6-like snRNA of the minor spliceosome, is a novel substrate for hMpn1. We unveil mechanistic details of a new U6 degradation pathway and further corroborate the notion that inefficient canonical and minor pre-mRNA splicing promotes PN.
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| |
|
| Overall design |
the 3' termini of human U6, U6atac and vtRNA1-1 transcripts from PN patient derived cells and from PN patient cells, compensated with hMPN1 were sequenced.
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| |
|
| Contributor(s) |
Shchepachev V, Soneson C |
| Citation missing |
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| Submission date |
Aug 07, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Claus M Azzalin |
| E-mail(s) |
claus.azzalin@bc.biol.ethz.ch
|
| Organization name |
ETH Zürich
|
| Department |
Institute of Biochemistry
|
| Street address |
Otto-Stern-Weg 3
|
| City |
Zürich |
| ZIP/Postal code |
8093 |
| Country |
Switzerland |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE60198 |
The Mpn1 exonuclease defines a novel spliceosomal snRNA decay pathway dependent on Rrp6 and Lsm2-8 complex |
|
| Relations |
| BioProject |
PRJNA257730 |
| SRA |
SRP045329 |
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