4.8 Article

Identification of LACTB2, a metallo-β-lactamase protein, as a human mitochondrial endoribonuclease

Journal

NUCLEIC ACIDS RESEARCH
Volume 44, Issue 4, Pages 1813-1832

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/nar/gkw050

Keywords

-

Funding

  1. Israel Science Foundation
  2. AbbVie
  3. Bayer Pharma AG
  4. Boehringer Ingelheim
  5. Canada Foundation for Innovation
  6. Genome Canada
  7. GlaxoSmithKline
  8. Janssen
  9. Lilly Canada
  10. Merck Co.
  11. Novartis Research Foundation
  12. Ontario Ministry of Economic Development and Innovation
  13. Pfizer
  14. Sao Paulo Research Foundation-FAPESP
  15. Takeda
  16. Wellcome Trust [092809/Z/10/Z]
  17. Wellcome Trust [092809/Z/10/Z] Funding Source: Wellcome Trust

Ask authors/readers for more resources

Post-transcriptional control of mitochondrial gene expression, including the processing and generation of mature transcripts as well as their degradation, is a key regulatory step in gene expression in human mitochondria. Consequently, identification of the proteins responsible for RNA processing and degradation in this organelle is of great importance. The metallo-beta-lactamase (MBL) is a candidate protein family that includes ribo- and deoxyribonucleases. In this study, we discovered a function for LACTB2, an orphan MBL protein found in mammalian mitochondria. Solving its crystal structure revealed almost perfect alignment of the MBL domain with CPSF73, as well as to other ribonucleases of the MBL superfamily. Recombinant human LACTB2 displayed robust endoribonuclease activity on ssRNA with a preference for cleavage after purine-pyrimidine sequences. Mutational analysis identified an extended RNA-binding site. Knockdown of LACTB2 in cultured cells caused a moderate but significant accumulation of many mitochondrial transcripts, and its overexpression led to the opposite effect. Furthermore, manipulation of LACTB2 expression resulted in cellular morphological deformation and cell death. Together, this study discovered that LACTB2 is an endoribonuclease that is involved in the turnover of mitochondrial RNA, and is essential for mitochondrial function in human cells.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available