Msc6p is required for mitochondrial translation initiation in the absence of formylated Met-tRNA(fMet)

Author(s)

Ribeiro Franco, Leticia Veloso ^[1] ; Moda, Bruno S. ^[1] ; Soares, Maria A. K. M. ^[1] ; Barros, Mario H. ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, Ave Prof Lineu Prestes 1374, BR-05508900 Sao Paulo - Brazil

• Document type: Journal article
• Source: FEBS Journal; v. 286, n. 7, p. 1407-1419, APR 2019.
• Web of Science Citations: 0

Abstract

Mitochondrial translation normally requires formylation of the initiator tRNA-met, a reaction catalyzed by the enzyme formyltransferase, Fmt1p and MTFMT in Saccharomyces cerevisiae and human mitochondria, respectively. Yeast fmt1 mutants devoid of Fmt1p, however, can synthesize all mitochondrial gene products by initiating translation with a non-formylated methionyl-tRNA. Yeast synthetic respiratory-deficient fmt1 mutants have uncovered several factors suggested to play a role in translation initiation with non-formylated methionyl-tRNA. Here, we present evidence that Msc6p, a member of the pentatricopeptide repeat (PPR) motif family, is another essential factor for mitochondrial translation in fmt1 mutants. The PPR motif is characteristic of RNA-binding proteins found in chloroplasts and plant and fungal mitochondria, and is generally involved in RNA stability and transport. Moreover, in the present study, we show that the respiratory deficiency of fmt1msc6 double mutants can be rescued by overexpression of the yeast mitochondrial initiation factor mIF-2, encoded by IFM1. The role of Msc6p in translational initiation is further supported by pull-down assays showing that it transiently interacts with mIF-2. Altogether, our data indicate that Msc6p is an important factor in mitochondrial translation with an auxiliary function related to the mIF-2-dependent formation of the initiation complex. (AU)

• FAPESP's process: 13/09482-8 - Saccharomyces cerevisiae as a model for mitochondrial translation studies
• Grantee: Mario Henrique de Barros
• Support type: Regular Research Grants
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 17/23921-5 - Study of mitochondrial translation factors
• Grantee: Mario Henrique de Barros
• Support type: Regular Research Grants
• FAPESP's process: 16/25907-7 - Search for the gene coding for the amidotransferase connecting subunit in humans and the study of the function of MSC6 in yeast
• Grantee: Maria Antônia Kfouri Martins Soares
• Support type: Scholarships in Brazil - Scientific Initiation