PMID- 24475367 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211021 IS - 2159-2543 (Print) IS - 2159-256X (Electronic) IS - 2159-2543 (Linking) VI - 3 IP - 6 DP - 2013 Nov 1 TI - Lost in translation: The biogenesis of non-LTR retrotransposon proteins. PG - e27525 LID - e27525 AB - "Young" APE-type non-LTR retrotransposons (non-LTRs) typically encode two open reading frames (ORFs 1 and 2). The shorter ORF1 translation product (ORF1p) comprises an RNA binding activity, thought to bind to non-LTR transcript RNA, protect against nuclease degradation and specify nuclear import of the ribonuclear protein complex (RNP). ORF2 encodes a multifunctional protein (ORF2p) comprising apurinic/apyrimidinic endonuclease (APE) and reverse-transcriptase (RT) activities, responsible for genome replication and re-integration into chromosomal DNA. However, some clades of APE-type non-LTRs only encode a single ORF-corresponding to the multifunctional ORF2p outlined above (and for simplicity referred-to as ORF2 below). The absence of an ORF1 correlates with the acquisition of a 2A oligopeptide translational recoding element (some 18-30 amino acids) into the N-terminal region of ORF2p. In the case of non-LTRs encoding two ORFs, the presence of ORF1 would necessarily downregulate the translation of ORF2. We argue that in the absence of an ORF1, 2A could provide the corresponding translational downregulation of ORF2. While multiple molecules of ORF1p are required to decorate the non-LTR transcript RNA in the cytoplasm, conceivably only a single molecule of ORF2p is required for target-primed reverse transcription/integration in the nucleus. Why would the translation of ORF2 need to be controlled by such mechanisms? An "excess" of ORF2p could result in disadvantageous levels of genome instability by, for example, enhancing short, interspersed, element (SINE) retrotransposition and the generation of processed pseudogenes. If so, the acquisition of mechanisms-such as 2A-to control ORF2p biogenesis would be advantageous. FAU - Luke, Garry A AU - Luke GA AD - Biomedical Sciences Research Complex; Fife, Scotland UK. FAU - Roulston, Claire AU - Roulston C AD - Biomedical Sciences Research Complex; Fife, Scotland UK. FAU - Odon, Valerie AU - Odon V AD - Biomedical Sciences Research Complex; Fife, Scotland UK. FAU - de Felipe, Pablo AU - de Felipe P AD - Biomedical Sciences Research Complex; Fife, Scotland UK. FAU - Sukhodub, Andriy AU - Sukhodub A AD - Biomedical Sciences Research Complex; Fife, Scotland UK. FAU - Ryan, Martin D AU - Ryan MD AD - Biomedical Sciences Research Complex; Fife, Scotland UK. LA - eng PT - Journal Article DEP - 20131213 PL - United States TA - Mob Genet Elements JT - Mobile genetic elements JID - 101564504 CON - Odon V, Luke GA, Roulston C, de Felipe P, Ruan L, Escuin-Ordinas H, Brown JD, Ryan MD, Sukhodub A. APE-type non-LTR retrotransposons of multicellular organisms encode virus-like 2A oligopeptide sequences, which mediate translational recoding during protein synthesis. Mol Biol Evol. 2013;30:1955-65. doi: 10.1093/molbev/mst102. PMC - PMC3894237 OTO - NOTNLM OT - 2A oligopeptide OT - non-LTR retrotransposons OT - retrotransposition OT - translational recoding EDAT- 2014/01/30 06:00 MHDA- 2014/01/30 06:01 PMCR- 2013/12/13 CRDT- 2014/01/30 06:00 PHST- 2013/10/16 00:00 [received] PHST- 2013/12/11 00:00 [revised] PHST- 2013/12/13 00:00 [accepted] PHST- 2014/01/30 06:00 [entrez] PHST- 2014/01/30 06:00 [pubmed] PHST- 2014/01/30 06:01 [medline] PHST- 2013/12/13 00:00 [pmc-release] AID - 2013MGE0031R [pii] AID - 10.4161/mge.27525 [doi] PST - ppublish SO - Mob Genet Elements. 2013 Nov 1;3(6):e27525. doi: 10.4161/mge.27525. Epub 2013 Dec 13.