Summary information and primary citation
- PDB-id
-
6sty;
DSSR-derived features in text and
JSON formats
- Class
- RNA binding protein
- Method
- X-ray (3.15 Å)
- Summary
- Human rexo2 exonuclease in complex with RNA.
- Reference
-
Szewczyk M, Malik D, Borowski LS, Czarnomska SD, Kotrys
AV, Klosowska-Kosicka K, Nowotny M, Szczesny RJ (2020):
"Human
REXO2 controls short mitochondrial RNAs generated by
mtRNA processing and decay machinery to prevent
accumulation of double-stranded RNA." Nucleic
Acids Res., 48, 5572-5590. doi:
10.1093/nar/gkaa302.
- Abstract
- RNA decay is a key element of mitochondrial RNA
metabolism. To date, the only well-documented machinery
that plays a role in mtRNA decay in humans is the complex
of polynucleotide phosphorylase (PNPase) and SUV3 helicase,
forming the degradosome. REXO2, a homolog of prokaryotic
oligoribonucleases present in humans both in mitochondria
and the cytoplasm, was earlier shown to be crucial for
maintaining mitochondrial homeostasis, but its function in
mitochondria has not been fully elucidated. In the present
study, we created a cellular model that enables the clear
dissection of mitochondrial and non-mitochondrial functions
of human REXO2. We identified a novel mitochondrial short
RNA, referred to as ncH2, that massively accumulated upon
REXO2 silencing. ncH2 degradation occurred independently of
the mitochondrial degradosome, strongly supporting the
hypothesis that ncH2 is a primary substrate of REXO2. We
also investigated the global impact of REXO2 depletion on
mtRNA, revealing the importance of the protein for
maintaining low steady-state levels of mitochondrial
antisense transcripts and double-stranded RNA. Our detailed
biochemical and structural studies provide evidence of
sequence specificity of the REXO2 oligoribonuclease. We
postulate that REXO2 plays dual roles in human
mitochondria, 'scavenging' nanoRNAs that are produced by
the degradosome and clearing short RNAs that are generated
by RNA processing.
