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Disease
[RT22_HUMAN] Hypotonia with lactic acidemia and hyperammonemia. The disease is caused by mutations affecting the gene represented in this entry. [RT16_HUMAN] Combined oxidative phosphorylation defect type 2. The disease is caused by mutations affecting the gene represented in this entry. [RM03_HUMAN] Combined oxidative phosphorylation defect type 9. The disease is caused by mutations affecting the gene represented in this entry. [RM44_HUMAN] Infantile hypertrophic cardiomyopathy due to MRPL44 deficiency. The disease is caused by mutations affecting the gene represented in this entry.
Function
[AKIP_HUMAN] May act as a negative regulator of Aurora-A kinase, by down-regulation through proteasome-dependent degradation. [RM14_HUMAN] Forms part of 2 intersubunit bridges in the assembled ribosome. Upon binding to MALSU1 intersubunit bridge formation is blocked, preventing ribosome formation and repressing translation (Probable).[1] [RT29_HUMAN] Involved in mediating interferon-gamma-induced cell death. [RM36_HUMAN] Component of the large subunit of the mitochondrial ribosome. [G45IP_HUMAN] Acts as a negative regulator of G1 to S cell cycle phase progression by inhibiting cyclin-dependent kinases. Inhibitory effects are additive with GADD45 proteins but occurs also in the absence of GADD45 proteins. Acts as a repressor of the orphan nuclear receptor NR4A1 by inhibiting AB domain-mediated transcriptional activity. May be involved in the hormone-mediated regulation of NR4A1 transcriptional activity. May play a role in mitochondrial protein synthesis. [RM16_HUMAN] Component of the large subunit of mitochondrial ribosome. [ICT1_HUMAN] Essential peptidyl-tRNA hydrolase component of the mitochondrial large ribosomal subunit. Acts as a codon-independent translation release factor that has lost all stop codon specificity and directs the termination of translation in mitochondrion, possibly in case of abortive elongation. May be involved in the hydrolysis of peptidyl-tRNAs that have been prematurely terminated and thus in the recycling of stalled mitochondrial ribosomes.[2] [PTCD3_HUMAN] Mitochondrial RNA-binding protein that has a role in mitochondrial translation.[3] [RM41_HUMAN] Component of the mitochondrial ribosome large subunit. Also involved in apoptosis and cell cycle. Enhances p53/TP53 stability, thereby contributing to p53/TP53-induced apoptosis in response to growth-inhibitory condition. Enhances p53/TP53 translocation to the mitochondria. Has the ability to arrest the cell cycle at the G1 phase, possibly by stabilizing the CDKN1A and CDKN1B (p27Kip1) proteins.[4] [5] [RM44_HUMAN] Component of the 39S subunit of mitochondrial ribosome. May have a function in the assembly/stability of nascent mitochondrial polypeptides exiting the ribosome.[6]
Publication Abstract from PubMed
The highly divergent ribosomes of human mitochondria (mitoribosomes) synthesize 13 essential proteins of oxidative phosphorylation complexes. We have determined the structure of the intact mitoribosome to 3.5 angstrom resolution by means of single-particle electron cryogenic microscopy. It reveals 80 extensively interconnected proteins, 36 of which are specific to mitochondria, and three ribosomal RNA molecules. The head domain of the small subunit, particularly the messenger (mRNA) channel, is highly remodeled. Many intersubunit bridges are specific to the mitoribosome, which adopts conformations involving ratcheting or rolling of the small subunit that are distinct from those seen in bacteria or eukaryotes. An intrinsic guanosine triphosphatase mediates a contact between the head and central protuberance. The structure provides a reference for analysis of mutations that cause severe pathologies and for future drug design.
Ribosome. The structure of the human mitochondrial ribosome.,Amunts A, Brown A, Toots J, Scheres SH, Ramakrishnan V Science. 2015 Apr 3;348(6230):95-8. doi: 10.1126/science.aaa1193. Epub 2015 Apr, 2. PMID:25838379[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hauser R, Pech M, Kijek J, Yamamoto H, Titz B, Naeve F, Tovchigrechko A, Yamamoto K, Szaflarski W, Takeuchi N, Stellberger T, Diefenbacher ME, Nierhaus KH, Uetz P. RsfA (YbeB) proteins are conserved ribosomal silencing factors. PLoS Genet. 2012;8(7):e1002815. doi: 10.1371/journal.pgen.1002815. Epub 2012 Jul , 19. PMID:22829778 doi:10.1371/journal.pgen.1002815
- ↑ Richter R, Rorbach J, Pajak A, Smith PM, Wessels HJ, Huynen MA, Smeitink JA, Lightowlers RN, Chrzanowska-Lightowlers ZM. A functional peptidyl-tRNA hydrolase, ICT1, has been recruited into the human mitochondrial ribosome. EMBO J. 2010 Mar 17;29(6):1116-25. doi: 10.1038/emboj.2010.14. Epub 2010 Feb 25. PMID:20186120 doi:http://dx.doi.org/10.1038/emboj.2010.14
- ↑ Davies SM, Rackham O, Shearwood AM, Hamilton KL, Narsai R, Whelan J, Filipovska A. Pentatricopeptide repeat domain protein 3 associates with the mitochondrial small ribosomal subunit and regulates translation. FEBS Lett. 2009 Jun 18;583(12):1853-8. Epub 2009 May 8. PMID:19427859 doi:http://dx.doi.org/S0014-5793(09)00357-3
- ↑ Yoo YA, Kim MJ, Park JK, Chung YM, Lee JH, Chi SG, Kim JS, Yoo YD. Mitochondrial ribosomal protein L41 suppresses cell growth in association with p53 and p27Kip1. Mol Cell Biol. 2005 Aug;25(15):6603-16. PMID:16024796 doi:http://dx.doi.org/25/15/6603
- ↑ Kim MJ, Yoo YA, Kim HJ, Kang S, Kim YG, Kim JS, Yoo YD. Mitochondrial ribosomal protein L41 mediates serum starvation-induced cell-cycle arrest through an increase of p21(WAF1/CIP1). Biochem Biophys Res Commun. 2005 Dec 16;338(2):1179-84. Epub 2005 Oct 21. PMID:16256947 doi:http://dx.doi.org/10.1016/j.bbrc.2005.10.064
- ↑ Carroll CJ, Isohanni P, Poyhonen R, Euro L, Richter U, Brilhante V, Gotz A, Lahtinen T, Paetau A, Pihko H, Battersby BJ, Tyynismaa H, Suomalainen A. Whole-exome sequencing identifies a mutation in the mitochondrial ribosome protein MRPL44 to underlie mitochondrial infantile cardiomyopathy. J Med Genet. 2013 Mar;50(3):151-9. doi: 10.1136/jmedgenet-2012-101375. Epub 2013 , Jan 12. PMID:23315540 doi:http://dx.doi.org/10.1136/jmedgenet-2012-101375
- ↑ Amunts A, Brown A, Toots J, Scheres SH, Ramakrishnan V. Ribosome. The structure of the human mitochondrial ribosome. Science. 2015 Apr 3;348(6230):95-8. doi: 10.1126/science.aaa1193. Epub 2015 Apr, 2. PMID:25838379 doi:http://dx.doi.org/10.1126/science.aaa1193
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