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Identification of small RNAs interacting with FLAG/HA(FH)-tagged LARP7

ABSTRACT: Identification of small RNAs interacting with FLAG/HA(FH)-tagged LARP7

PROVIDER: PRJNA522460 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8580082.fastq.gz	Fastqsanger.gz
	SRR8580083.fastq.gz	Fastqsanger.gz
	SRR8580084.fastq.gz	Fastqsanger.gz

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Identification of small RNAs interacting with FLAG/HA(FH)-tagged LARP7

Project description: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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