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KREPA6 functions in RNA editing catalytic complex structural organization and gRNA utilization in Trypanosoma brucei.

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Stunning Intricacies of RNA Editing Complexes RECC, RESC, and REH2C: Functional Organization, Developmental Regulation, and Evolutionary History in Kinetoplastid Protists.

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KRGG1 function in RNA editing in Trypanosoma brucei.

Jason Carnes1, Claire Gendrin1, Suzanne M McDermott1

  • 1Seattle Children's Research Institute, Seattle, Washington 98109, USA.

RNA (New York, N.Y.)
|November 18, 2022
PubMed
Summary

KRGG1 is essential for mitochondrial RNA editing in trypanosomes, coordinating guide RNA (gRNA) editing complexes. Its disruption impairs mRNA maturation, highlighting its critical role in parasite survival.

Keywords:
RESCRGGRNA bindingRNA editingmitochondriatrypanosomes

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Area of Science:

  • Molecular Biology
  • Parasitology
  • Genetics

Background:

  • Mitochondrial gene expression in trypanosomes relies on unique multiprotein complexes for RNA editing.
  • RNA editing catalytic complexes (RECCs) and RNA editing substrate-binding complexes (RESCs) are crucial for mitochondrial mRNA maturation.
  • The precise function of RESCs and the role of KRGG1 in RNA editing were previously uncertain.

Purpose of the Study:

  • To investigate the essentiality and function of KRGG1 in trypanosome mitochondrial RNA editing.
  • To elucidate the relationship between KRGG1, RESCs, and the RNA editing process.
  • To determine the structural and functional significance of KRGG1's homology with RESC6.

Main Methods:

  • Functional analysis of KRGG1 in BF parasites, including repression studies.
  • Analysis of edited mRNA levels (A6 and ND8) following KRGG1 manipulation.
  • Sequence and structure analysis of KRGG1, including homology searches and assessment of mutated protein function.

Main Results:

  • KRGG1 is essential for normal RNA editing in BF parasites.
  • KRGG1 repression leads to decreased edited A6 mRNA and increased edited ND8 mRNA.
  • A conserved ARM/HEAT-like motif in KRGG1 is critical for its function and association with RESCs.

Conclusions:

  • KRGG1 plays a critical role in trypanosome mitochondrial RNA editing.
  • KRGG1's function is intrinsically linked to RESC activity, likely acting as a scaffold or facilitator.
  • Understanding KRGG1's mechanism provides insights into the complex regulation of kinetoplastid mitochondrial gene expression.