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| Status |
Public on Feb 03, 2020 |
| Title |
Identification of small RNAs interacting with LARP7 |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
The La-related protein LARP7 has been mainly described as a component of the 7SK small nuclear ribonucleoprotein (snRNP) complex, which negatively regulates RNA polymerase II by sequestering the positive transcription elongation factor b (P-TEFb). In our studies, we discovered a novel, 7SK snRNP-independent function of LARP7. We show that LARP7 interacts with the U6 spliceosomal RNA as well as with the small nucleolar RNAs (snoRNAs) directing the 2'-O-methylations of U6. Importantly, in the absence of LARP7, significantly less 2'-O-methylations are deposited on U6 affecting splicing fidelity. Mutations in the LARP7 gene have been associated with the Alazami syndrome, a form of primordial dwarfism characterized by intellectual disability. We describe a novel loss-of-function mutation of LARP7 occurring in Alazami patients and detect reduced 2'-O-methylations of U6 in patient-derived samples. Thus, aberrant posttranscriptional RNA modifications of the spliceosomal U6 snRNA may contribute to the development of this severe disease.
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| Overall design |
Identification of small RNAs interacting with endogenous LARP7 by immunoprecipitations and comparison of the enrichment over an input sample.
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| Contributor(s) |
Hasler D, Lehmann G, Eichner N, Meister G |
| Citation(s) |
32017898 |
| Submission date |
Feb 14, 2019 |
| Last update date |
Feb 19, 2020 |
| Contact name |
Gerhard Lehmann |
| E-mail(s) |
gerhard.lehmann@vkl.uni-regensburg.de
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| Organization name |
University of Regensburg
|
| Department |
Biochemistry 1
|
| Street address |
Universitaetsstrasse 31
|
| City |
Regensburg |
| ZIP/Postal code |
93053 |
| Country |
Germany |
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| Platforms (1) |
| GPL15433 |
Illumina HiSeq 1000 (Homo sapiens) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE126911 |
The Alazami Syndrome-associated protein LARP7 guides U6 small nuclear RNA modification and contributes to splicing robustness |
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| Relations |
| BioProject |
PRJNA522462 |
| SRA |
SRP185934 |
