Maturation of selected human mitochondrial tRNAs requires deadenylation

Area of Science:

• Mitochondrial biology
• Molecular genetics
• RNA biology

Background:

• Human mitochondria utilize a unique genome (mtDNA) encoding key oxidative phosphorylation proteins.
• mtDNA expression involves intricate RNA processing and maturation steps.
• RNA quality control mechanisms in human mitochondria remain incompletely understood.

Purpose of the Study:

• To investigate RNA quality control pathways in human mitochondria.
• To identify factors involved in the maturation of mitochondrial non-coding RNAs.
• To elucidate the functional consequences of aberrant mitochondrial RNA processing.

Main Methods:

• Mitochondrial ribosome profiling combined with mitochondrial poly(A)-tail RNA sequencing (MPAT-Seq).
• Analysis of RNA processing and polyadenylation in wild-type and PDE12-deficient cells.
• Assessment of mitoribosome integrity and mt-tRNA aminoacylation levels.

Main Results:

• PDE12 was identified as a key exoribonuclease in mitochondrial RNA quality control.
• Loss of PDE12 resulted in spurious polyadenylation of mt-rRNA and mt-tRNA.
• Aberrant mt-tRNA polyadenylation reduced aminoacylation and caused mitoribosome stalling.

Conclusions:

• A novel deadenylation-dependent mitochondrial RNA maturation pathway involving PDE12 was uncovered.
• PDE12 plays a critical role in maintaining the fidelity of mitochondrial non-coding RNAs.
• Dysfunctional RNA processing in mitochondria can directly impact translation and cellular respiration.