PMID- 18993075 OWN - NLM STAT- MEDLINE DCOM- 20090127 LR - 20131121 IS - 0960-9822 (Print) IS - 0960-9822 (Linking) VI - 18 IP - 22 DP - 2008 Nov 25 TI - Evidence for insertional RNA editing in humans. PG - 1760-5 LID - 10.1016/j.cub.2008.09.059 [doi] AB - Large-scale analysis directly at the protein level holds the promise of uncovering features not apparent or present at the gene level [1-3]. Although mass spectrometry (MS)-based proteomics can now identify and quantify thousands of cellular proteins in large-scale proteomics experiments, much of the peptide information contained in these experiments remains unassigned [4]. Here, we use such information to discover a previously unreported mechanism creating altered protein forms. Linker histones H1 and high-mobility group (HMG) proteins are abundant nuclear proteins that regulate gene expression through modulation of chromatin structure [5-8]. In the high-resolution MS analysis of histone H1 and HMG protein fractions isolated from human cells, we discovered peptides that mapped upstream of the known translation start sites of these genes. No alternative upstream start site exists in the genome, but analysis of Expressed Sequence Tag (EST) databases revealed that these N-terminally extended (ET) proteins are due to in-frame translation of the 5' untranslated region (5'UTR) sequences of the transcripts. The new translation start sites are created by a single uridine insertion between AG, reflecting a previously unreported RNA-editing mechanism. To our knowledge, this is the first report of RNA-insertion editing in humans and may be an example of the type of discoveries possible with modern proteomics methods. FAU - Zougman, Alexandre AU - Zougman A AD - Department of Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany. FAU - Ziolkowski, Piotr AU - Ziolkowski P FAU - Mann, Matthias AU - Mann M FAU - Wisniewski, Jacek R AU - Wisniewski JR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20081106 PL - England TA - Curr Biol JT - Current biology : CB JID - 9107782 RN - 0 (5' Untranslated Regions) RN - 63231-63-0 (RNA) RN - WHI7HQ7H85 (Uridine) SB - IM MH - 5' Untranslated Regions MH - Amino Acid Sequence MH - Base Sequence MH - Expressed Sequence Tags MH - Genome, Human MH - HeLa Cells MH - Humans MH - Molecular Sequence Data MH - Protein Biosynthesis/physiology MH - Proteomics MH - RNA/chemistry MH - RNA Editing/*physiology MH - Sequence Analysis, RNA MH - Uridine/chemistry/genetics EDAT- 2008/11/11 09:00 MHDA- 2009/01/28 09:00 CRDT- 2008/11/11 09:00 PHST- 2008/06/27 00:00 [received] PHST- 2008/08/28 00:00 [revised] PHST- 2008/09/19 00:00 [accepted] PHST- 2008/11/11 09:00 [pubmed] PHST- 2009/01/28 09:00 [medline] PHST- 2008/11/11 09:00 [entrez] AID - S0960-9822(08)01294-3 [pii] AID - 10.1016/j.cub.2008.09.059 [doi] PST - ppublish SO - Curr Biol. 2008 Nov 25;18(22):1760-5. doi: 10.1016/j.cub.2008.09.059. Epub 2008 Nov 6.