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PMID: 18413600 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Identification and evolution of fungal mitochondrial tyrosyl-tRNA synthetases with group I intron splicing activity.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 105 ·No. 16 ·2008-04-22 ·Pages 6010-5

Paukstelis PJ, Lambowitz AM

Abstract

The bifunctional Neurospora crassa mitochondrial tyrosyl-tRNA synthetase (CYT-18 protein) both aminoacylates mitochondrial tRNA(Tyr) and acts as a structure-stabilizing splicing cofactor for group I introns. Previous studies showed that CYT-18 has distinct tRNA(Tyr) and group I intron-binding sites, with the latter formed by three small "insertions" in the nucleotide-binding fold and other structural adaptations compared with nonsplicing bacterial tyrosyl-tRNA synthetases. Here, analysis of genomic sequences shows that mitochondrial tyrosyl-tRNA synthetases with structural adaptations similar to CYT-18's are uniquely characteristic of fungi belonging to the subphylum Pezizomycotina, and biochemical assays confirm group I intron splicing activity for the enzymes from several of these organisms, including Aspergillus nidulans and the human pathogens Coccidioides posadasii and Histoplasma capsulatum. By combining multiple sequence alignments with a previously determined cocrystal structure of a CYT-18/group I intron RNA complex, we identify conserved features of the Pezizomycotina enzymes related to group I intron and tRNA interactions. Our results suggest that mitochondrial tyrosyl-tRNA synthetases with group I intron splicing activity evolved during or after the divergence of the fungal subphyla Pezizomycotina and Saccharomycotina by a mechanism involving the concerted differentiation of preexisting protein loop regions. The unique group I intron splicing activity of these fungal enzymes may provide a new target for antifungal drugs.

MeSH Terms
Alternative Splicing Amino Acid Sequence Antifungal Agents/chemistry,pharmacology Aspergillus nidulans/enzymology,genetics Coccidioides/enzymology,genetics Conserved Sequence Evolution, Molecular Fungal Proteins/chemistry,genetics,metabolism Histoplasma/enzymology,genetics Introns/genetics Mitochondria/enzymology Mitochondrial Proteins/chemistry,genetics,metabolism Molecular Sequence Data Mutagenesis, Insertional Neurospora crassa/enzymology,genetics Protein Conformation RNA, Fungal/genetics,metabolism Sequence Alignment Sequence Analysis, Protein Tyrosine/metabolism Tyrosine-tRNA Ligase/chemistry,genetics,metabolism
Chemicals
Antifungal Agents Fungal Proteins Mitochondrial Proteins RNA, Fungal Tyrosine Tyrosine-tRNA Ligase
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Paukstelis Paul J
Institute for Cellular and Molecular Biology, Department of Chemistry and Biochemistry, and Section of Molecular Genetics and Microbiology, School of Biological Sciences, University of Texas, Austin, TX 78712, USA.
Lambowitz Alan M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0801722105
Published
2008-04-22
Epub
2008-00-14
Pages
6010-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2329719
Subset
IM
Grants
NIGMS NIH HHS · R01 GM037951 · United States
NIGMS NIH HHS · R37 GM037951 · United States
NIGMS NIH HHS · GM037951 · United States
External Links
PubMed source DOI: 10.1073/pnas.0801722105 PMC Full Text View journal details
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