RMRP (RNA component of mitochondrial RNA processing endoribonuclease)

Other names	CHH
	RMRPR
HGNC (Hugo)	RMRP
Location	9p21-p12
	Figure 1: Cartoon of the RMRP genomic gene structure. The RMRP gene is an intronless gene that is 267 bp long (violet). The promoter region contains a SP1 binding site (blue), an octamer (red), a proximal sequence element (PSE) (green) and a TATA box (yellow).

Note	RMRP is the RNA component of the RNase MRP protein complex. It functions as a RNA and is not translated into a protein.
	Figure 2: Expression pattern of the Rmrp gene. A: in situ hybridization of an E15.5 mouse embryo B: adult human Multiple tissue Northern Blot. Rmrp is ubiquitously expressed in human and mouse. H: hypertrophic chondrocytes.
Transcription	The RMRP gene is transcribed by the DNA dependent RNA polymerase III. The gene contains typical sequence elements of a RNA Pol III type 3 promoter. The core sequence elements such as the PSE element and a TATA box can be found upstream of the transcription initiation site of the RMRP gene. In addition, transcription factor binding sites like a SP1 binding element and an octamer (recruits the transcription factor Oct-1) sequence could serve as distal sequence elements (DSE) to enhance the transcription of RMRP similar to the DSE element of the human U6 snRNA gene. Expression RMRP is strongly and ubiquitously expressed in mouse embryos (as an example an E15.5 mouse embryo is shown). In bone Rmrp is more strongly expressed in hypertrophic chondrocytes and pericondrium than in the zone of proliferating chondrocytes. There is also very strong expression in the epiphysis. In humans RMRP shows also a very strong expression in adult tissues. A little weaker expression is observed in skeletal muscle when compared to the GAPDH hybridization control. In Xenopus laevis oocytes RMRP is stronger expressed in developmental stages with a higher content of mitochondria. Function RMRP has been mostly studied in yeast and multiple functions have been attributed to this ribonucleoprotein complex, called RNase MRP. The yeast orthologues gene is called nme1. Firstly, it plays a role in mitochondrial DNA replication. It cleaves the RNA primer of RNA/DNA hybrid. This hybrid formation initiates the mitochondrial DNA replication. It is also involved in the RNA primer formation. Secondly, RMRP is involved in the progression of the cell cycle at the end of mitosis. Some nme1 mutants arrest in the late cycle of mitosis. These mutants present morphologically as large budded cells with dumbbell-shaped nuclei, and also exhibit extended spindles. This cell cycle arrest might be due to an increased level of CLB2. In wild type yeast strains the 5'UTR of CLB2 is cleaved by the RNase MRP complex. This causes a rapid degradation of the CLB2 mRNA, which leads to a cell cycle progression. Thirdly, RMRP also plays a role in the ribosomal RNA processing. In yeast, it cleaves pre-ribosomal RNA at the A3 site thus helps the maturation of the short and active form of the 5.8S rRNA. Homology RNase P is also a ribonucleoprotein endoribonuclease that is mainly involved in tRNA precursor maturation. RNase P and RNase MRP have eight proteins in common. The protein RPR2p is unique to the RNase P complex. In yeast two RNase MRP specific proteins have been identified; snm1 and rmp1. The loss of function of snm1 leads to a defect in the chromosome segregation during mitosis. But the exact mechanism is not understood yet.

	Figure 3: Cartoon of the ribosomal RNA processing. If Rnase MRP cleaves the 27SA2 rRNA at the A3 site, this leads to the formation of the short form of the 5.8S rRNA (5.8SS). In a second, less effective alternative pathway, the 27SA2 rRNA is directly cleaved at the B1L site that leads at the end to the formation of the long form of the 5.8S rRNA (5.8SL).

Entity	Cartilage Hair Hypoplasia (CHH)
Prognosis	The adult height ranges between 111 and 151 cm in males and between 104 and 137 cm in females. Around 20% of Cartilage Hair Hypoplasia patients exhibit recurrent to severe infections. These patients show evidence of immune deficiency in vivo and in vitro.
Oncogenesis	A predisposition to certain cancers primarily lymphomas has been reported.

Search in all EBI   NCBI