====== MRPS25 ======

28S [[ribosomal protein]] S25, mitochondrial is a [[protein]] that in humans is encoded by the MRPS25 gene.

Mammalian mitochondrial ribosomal proteins are encoded by [[nuclear gene]]s and help in [[protein synthesis]] within the mitochondrion. Mitochondrial ribosomes ([[mitoribosome]]s) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to [[rRNA]] composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 28S subunit protein. A pseudogene corresponding to this gene is found on chromosome 4.
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[[Mitochondria]]l disorders are clinically and genetically heterogeneous, and are associated with a variety of disease mechanisms. Defects of mitochondrial [[protein synthesis]] account for the largest subgroup of disorders manifesting with impaired [[respiratory chain]] capacity; yet, only a few have been linked to dysfunction in the protein components of the mitochondrial ribosomes. 

Bugiardini et al., reported a subject presenting with dyskinetic [[cerebral palsy]] and partial [[agenesis of the corpus callosum]], while histochemical and biochemical analyses of skeletal muscle revealed signs of [[mitochondrial myopathy]]. Using [[exome sequencing]], they identified a [[homozygous]] variant, c.215C>T, in MRPS25, which encodes for a structural component of the 28S small subunit of the mitochondrial ribosome (mS25). The variant segregates with the disease, and substitutes a highly conserved proline residue with leucine (p.P72L) that, based on the high resolution structure of the 28S ribosome, is predicted to compromise inter-protein contacts and destabilize the small subunit. Concordant with the in silico analysis, patient's fibroblasts showed decreased levels of MRPS25 and other components of the 28S subunit. Moreover, mutant fibroblasts showed a dearth of the 28S assembly accompanied by impaired mitochondrial translation and decreased levels of multiple respiratory chain subunits. Crucially, these abnormalities were rescued by transgenic expression of wild-type MRPS25 in the mutant fibroblasts. Collectively, this data demonstrated the pathogenicity of the p.P72L variant, and identified MRPS25 as a new cause of mitochondrial translation defect
((Bugiardini E, Mitchell AL, Rosa ID, Horning-Do HT, Pitmann A, Poole OV, Holton
JL, Shah S, Woodward C, Hargreaves I, Quinlivan R, Amunts A, Wiesner RJ, Houlden 
H, Holt IJ, Hanna MG, Pitceathly RDS, Spinazzola A. MRPS25 mutations impair
mitochondrial translation and cause encephalomyopathy. Hum Mol Genet. 2019 Apr
30. pii: ddz093. doi: 10.1093/hmg/ddz093. [Epub ahead of print] PubMed PMID:
31039582.
)).