title: Polypeptide release factors and stop codon recognition in the apicoplast and mitochondrion of Plasmodium falciparum.
abstract: Correct termination of protein synthesis would be a critical step in translation of organellar open reading frames (ORFs) of the apicoplast and mitochondrion of the malaria parasite. We identify release factors (RFs) responsible for recognition of the UAA and UGA stop-codons of apicoplast ORFs and the sole UAA stop-codon that terminates translation from the three mitochondrial ORFs. A single nuclear-encoded canonical RF2, PfRF2Api , localizes to the apicoplast. It has a conserved tripeptide motif (SPF) for stop-codon recognition and is sufficient for peptidyl-tRNA hydrolysis (PTH) from both UAA and UGA. Two RF family proteins are targeted to the parasite mitochondrion; a canonical RF1, PfRF1Mit , with a variant codon-recognition motif (PxN instead of the conserved RF1 PxT) is the major peptidyl-hydrolase with specific recognition of the UAA codon relevant to mitochondrial ORFs. Mutation of the N residue of the PfRF1Mit PxN motif and two other conserved residues of the codon recognition domain lowers PTH activity from pre-termination ribosomes indicating their role in codon-recognition. The second RF imported by the mitochondrion is the non-canonical PfICT1 that functions as a dimer and mediates codon nonspecific peptide release. Our results help delineate a critical step in organellar translation in Plasmodium, which is an important target for anti-malarials.
authors.affiliation: Division of Molecular and Structural Biology, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Suniti
authors.initials: S
authors.lastname: Vaishya
authors.affiliation: Division of Molecular and Structural Biology, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Vikash
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Division of Molecular and Structural Biology, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Ankit
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Division of Molecular and Structural Biology, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Mohammad Imran
authors.initials: MI
authors.lastname: Siddiqi
authors.affiliation: Division of Molecular and Structural Biology, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Saman
authors.initials: S
authors.lastname: Habib
mesh_terms: D063546:Apicoplasts / Q000235:genetics / Q000378:metabolism; D018388:Codon, Terminator; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D010454:Peptide Termination Factors / Q000235:genetics* / Q000378:metabolism; D010963:Plasmodium falciparum / Q000235:genetics* / Q000378:metabolism; D012346:RNA, Transfer, Amino Acyl / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism
chemical_list: D018388:Codon, Terminator; D010454:Peptide Termination Factors; D012346:RNA, Transfer, Amino Acyl; C019037:tRNA, peptidyl-