LARP7

LARP7 is a protein which is found in the 7SK snRNP (small nuclear ribonucleoprotein). This snRNP complex inhibits a cyclin-dependent kinase, positive transcription elongation factor b, which is required for paused RNA polymerase II at a promoter to begin transcription elongation. A pseudogene of this gene is located on chromosome 3. Alternative splicing results in multiple transcript variants. Diseases associated with LARP7 include Alazami Syndrome and Med23. Gene Ontology (GO) annotations related to this gene include nucleic acid binding and RNA binding. An important paralog of this gene is LARP6. LARP7 is a negative transcriptional regulator of polymerase II genes, acting by means of the 7SK RNP system.

La ribonucleoprotein domain family, member 7

RNA-binding protein that specifically binds distinct small nuclear RNA (snRNAs) and regulates their processing and function (PubMed:18249148, PubMed:32017898).
Specifically binds the 7SK snRNA (7SK RNA) and acts as a core component of the 7SK ribonucleoprotein (RNP) complex, thereby acting as a negative regulator of transcription elongation by RNA polymerase II (PubMed:18249148, PubMed:18483487).
The 7SK RNP complex sequesters the positive transcription elongation factor b (P-TEFb) in a large inactive 7SK RNP complex preventing RNA polymerase II phosphorylation and subsequent transcriptional elongation (PubMed:18249148, PubMed:18483487).
The 7SK RNP complex also promotes snRNA gene transcription by RNA polymerase II via interaction with the little elongation complex (LEC) (PubMed:28254838).
LARP7 specifically binds to the highly conserved 3'-terminal U-rich stretch of 7SK RNA; on stimulation, remains associated with 7SK RNA, whereas P-TEFb is released from the complex (PubMed:18483487, PubMed:18281698).
LARP7 also acts as a regulator of mRNA splicing fidelity by promoting U6 snRNA processing (PubMed:32017898).
Specifically binds U6 snRNAs and associates with a subset of box C/D RNP complexes: promotes U6 snRNA 2'-O-methylation by facilitating U6 snRNA loading into box C/D RNP complexes (PubMed:32017898).
U6 snRNA 2'-O-methylation is required for mRNA splicing fidelity (PubMed:32017898).
Binds U6 snRNAs with a 5'-CAGGG-3' sequence motif (PubMed:32017898).
U6 snRNA processing is required for spermatogenesis (By similarity).

Box C/D RNA 3'-end processingManual Assertion Based On ExperimentIMP:UniProtKB
Cell differentiationIEA:UniProtKB-KW
mRNA processingIEA:UniProtKB-KW
Negative regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIMP:FlyBase
Negative regulation of transcription elongation from RNA polymerase II promoter1 PublicationIC:FlyBase
Negative regulation of viral transcriptionManual Assertion Based On ExperimentIMP:FlyBase
Positive regulation of protein localization to Cajal bodyManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of snRNA transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of mRNA splicing, via spliceosomeManual Assertion Based On ExperimentIMP:UniProtKB
RNA splicingIEA:UniProtKB-KW
SpermatogenesisISS:UniProtKB
U6 2'-O-snRNA methylationManual Assertion Based On ExperimentIMP:UniProtKB

Nucleus, nucleoplasm

Alazami syndrome (ALAZS):
A syndromic form of primordial dwarfism, a condition characterized by severe growth restriction that has its onset in utero, and results in short stature and undersize. ALAZS patients manifest severe intellectual disability and distinct facial features including malar hypoplasia, deep-set eyes, broad nose, short philtrum, and macrostomia. Some patients have non-specific and inconsistent skeletal findings, for example, scoliosis and mild epiphyseal changes in the proximal phalanges, but no frank dysplasia.