5oom

Structural highlights

Disease

[RM44_HUMAN] Infantile hypertrophic cardiomyopathy due to MRPL44 deficiency. 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.

Function

[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.^{[1] [2]} [ACPM_HUMAN] Carrier of the growing fatty acid chain in fatty acid biosynthesis in mitochondria. Accessory and non-catalytic subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), which functions in the transfer of electrons from NADH to the respiratory chain (By similarity). [RM18_HUMAN] Together with thiosulfate sulfurtransferase (TST), acts as a mitochondrial import factor for the cytosolic 5S rRNA. The precursor form shows RNA chaperone activity; is able to fold the 5S rRNA into an import-competent conformation that is recognized by rhodanese (TST). Both the cytoplasmic and mitochondrial forms are able to bind to the helix IV-loop D in the gamma domain of the 5S rRNA.^[3] [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. [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).^[4] [MASU1_HUMAN] May function as a ribosomal silencing factor. Addition to isolated mitochondrial ribosomal subunits partially inhibits translation. Interacts with mitochondrial ribosomal protein L14 (MRPL14), probably blocking formation of intersubunit bridge B8, preventing association of the 28S and 39S ribosomal subunits and the formation of functional ribosomes, thus repressing translation. May also participate in the assembly and/or regulation of the stability of the large subunit of the mitochondrial ribosome.^[5] [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.^[6] [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.^[7] [RM16_HUMAN] Component of the large subunit of mitochondrial ribosome.

References

1. ↑ 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
2. ↑ 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
3. ↑ Smirnov A, Entelis N, Martin RP, Tarassov I. Biological significance of 5S rRNA import into human mitochondria: role of ribosomal protein MRP-L18. Genes Dev. 2011 Jun 15;25(12):1289-305. doi: 10.1101/gad.624711. PMID:21685364 doi:http://dx.doi.org/10.1101/gad.624711
4. ↑ 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
5. ↑ Rorbach J, Gammage PA, Minczuk M. C7orf30 is necessary for biogenesis of the large subunit of the mitochondrial ribosome. Nucleic Acids Res. 2012 May;40(9):4097-109. doi: 10.1093/nar/gkr1282. Epub 2012, Jan 11. PMID:22238376 doi:http://dx.doi.org/10.1093/nar/gkr1282
6. ↑ 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
7. ↑ 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
8. ↑ Brown A, Rathore S, Kimanius D, Aibara S, Bai XC, Rorbach J, Amunts A, Ramakrishnan V. Structures of the human mitochondrial ribosome in native states of assembly. Nat Struct Mol Biol. 2017 Sep 11. doi: 10.1038/nsmb.3464. PMID:28892042 doi:http://dx.doi.org/10.1038/nsmb.3464