PMID- 19109895 OWN - NLM STAT- MEDLINE DCOM- 20090112 LR - 20240109 IS - 1097-4172 (Electronic) IS - 0092-8674 (Print) IS - 0092-8674 (Linking) VI - 135 IP - 7 DP - 2008 Dec 26 TI - Translation initiation on mammalian mRNAs with structured 5'UTRs requires DExH-box protein DHX29. PG - 1237-50 LID - 10.1016/j.cell.2008.10.037 [doi] AB - Eukaryotic protein synthesis begins with assembly of 48S initiation complexes at the initiation codon of mRNA, which requires at least seven initiation factors (eIFs). First, 43S preinitiation complexes comprising 40S ribosomal subunits, eIFs 3, 2, 1, and 1A, and tRNA(Met)(i) attach to the 5'-proximal region of mRNA and then scan along the 5' untranslated region (5'UTR) to the initiation codon. Attachment of 43S complexes is mediated by three other eIFs, 4F, 4A, and 4B, which cooperatively unwind the cap-proximal region of mRNA and later also assist 43S complexes during scanning. We now report that these seven eIFs are not sufficient for efficient 48S complex formation on mRNAs with highly structured 5'UTRs, and that this process requires the DExH-box protein DHX29. DHX29 binds 40S subunits and hydrolyzes ATP, GTP, UTP, and CTP. NTP hydrolysis by DHX29 is strongly stimulated by 43S complexes and is required for DHX29's activity in promoting 48S complex formation. FAU - Pisareva, Vera P AU - Pisareva VP AD - Department of Microbiology and Immunology, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA. FAU - Pisarev, Andrey V AU - Pisarev AV FAU - Komar, Anton A AU - Komar AA FAU - Hellen, Christopher U T AU - Hellen CU FAU - Pestova, Tatyana V AU - Pestova TV LA - eng GR - R01 GM059660/GM/NIGMS NIH HHS/United States GR - AI051340/AI/NIAID NIH HHS/United States GR - R01 AI051340/AI/NIAID NIH HHS/United States GR - GM059660/GM/NIGMS NIH HHS/United States GR - R01 AI051340-06A1/AI/NIAID NIH HHS/United States GR - R01 GM059660-08/GM/NIGMS NIH HHS/United States GR - R56 AI051340/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Cell JT - Cell JID - 0413066 RN - 0 (5' Untranslated Regions) RN - 0 (RNA, Messenger) RN - EC 2.7.7.- (DHX29 protein, human) RN - EC 3.6.4.13 (RNA Helicases) SB - IM MH - *5' Untranslated Regions MH - Animals MH - HeLa Cells MH - Humans MH - *Protein Biosynthesis MH - RNA Helicases/*metabolism MH - RNA, Messenger/*genetics MH - Rabbits MH - Reticulocytes/metabolism PMC - PMC2948571 MID - NIHMS85705 EDAT- 2008/12/27 09:00 MHDA- 2009/01/13 09:00 PMCR- 2010/10/01 CRDT- 2008/12/27 09:00 PHST- 2008/05/01 00:00 [received] PHST- 2008/08/01 00:00 [revised] PHST- 2008/10/21 00:00 [accepted] PHST- 2008/12/27 09:00 [entrez] PHST- 2008/12/27 09:00 [pubmed] PHST- 2009/01/13 09:00 [medline] PHST- 2010/10/01 00:00 [pmc-release] AID - S0092-8674(08)01374-3 [pii] AID - 10.1016/j.cell.2008.10.037 [doi] PST - ppublish SO - Cell. 2008 Dec 26;135(7):1237-50. doi: 10.1016/j.cell.2008.10.037.