EXOSC5
Description
The EXOSC5 (exosome component 5) is a protein-coding gene located on chromosome 19.
EXOSC5, also known as Exosome component 5, is a human gene that is part of the exosome complex. Mutations in EXOSC5 can cause autosomal recessive cerebellar ataxia, brain abnormalities, and cardiac conduction defects (CABAC). Individuals with CABAC often exhibit delayed developmental milestones, intellectual disability, cerebellar ataxia, hypotonia, dysarthria, and dysmorphic facies. Cardiac abnormalities include conduction defects, right bundle branch block, sinus node dysfunction, intraventricular conduction delay, atrioventricular block, and/or ventricular tachycardia. Cardiac pacemakers and defibrillators have been necessary in some cases, and sudden cardiac death has been reported. EXOSC5 interacts with Exosome component 1 and Exosome component 8.
EXOSC5 is a non-catalytic component of the RNA exosome complex, which possesses 3'->5' exoribonuclease activity and plays a crucial role in various cellular RNA processing and degradation events. Within the nucleus, the RNA exosome complex ensures proper maturation of stable RNA species such as rRNA, snRNA, and snoRNA. It also eliminates RNA processing by-products and non-coding transcripts, including antisense RNA species and promoter-upstream transcripts (PROMPTs), and mRNAs with processing defects, thereby restricting or preventing their export to the cytoplasm. The RNA exosome may participate in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by directing AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover, specifically degrading inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions. It also plays a role in RNA surveillance pathways, preventing translation of aberrant mRNAs. EXOSC5 seems to be involved in the degradation of histone mRNA. The catalytically inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to be critical for RNA binding and presentation for ribonucleolysis, and acts as a scaffold for the association with catalytic subunits and accessory proteins or complexes. In vitro, EXOSC5 does not bind or digest single-stranded RNA and binds to double-stranded DNA without detectable DNase activity. {ECO:0000269|PubMed:11782436, ECO:0000269|PubMed:20660080, ECO:0000269|PubMed:21269460}
EXOSC5 is also known as CABAC, RRP41B, RRP46, Rrp46p, hRrp46p, p12B.
