RNase P

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Crystal structure of RNase P with substrate tRNA (green), PDB 2A64
Crystal structure of RNase P with substrate tRNA (green), PDB 2A64

Ribonuclease P (RNase P) is a type of Ribonuclease that is currently under heavy research. RNase P is unique from other RNases in that it is a ribozyme – a ribonucleic acid that acts as a catalyst in the same way that a protein based enzyme would. Its function is to cleave off an extra, or precursor, sequence of RNA on tRNA molecules [1]. Further RNase P is one of two known multiple turnover ribozymes in nature (the other being the ribosome), the discovery of which earned Professor Sidney Altman the Nobel Prize in Chemistry in 1989. In fact, Sidney Altman discovered the existence of precursor tRNA with flanking sequences and was the first to characterize RNase P and its activity in processing of the 5' leader sequence of precursor tRNA back in the 70's. Recent findings also reveal that RNase P has a new function [2]. It has been shown that human nuclear RNase P is required for the normal and efficient transcription of various small noncoding RNA genes, such as tRNA, 5S rRNA, SRP RNA and U6 snRNA genes [3], which are transcribed by RNA polymerase III, one of three major nuclear RNA polymerases in human cells.

Contents

[edit] In bacteria

Further information: Bacterial RNase P class A and Bacterial RNase P class B

In bacteria, such as E. coli, RNase P has two components: an RNA chain, called M1 RNA, and a polypeptide chain, or protein, called C5 protein [4], [5]. In vivo, both components are necessary for the ribozyme to function properly, but in vitro, the M1 RNA can act alone as a catalyst [1]. The primary role of the C5 protein is to enhance the substrate binding affinity and the catalytic rate of the M1 RNA enzyme probably by increasing the metal ion affinity in the active site. The crystal structure of bacterial RNase P RNA has been recently resolved, revealing its flat surface that is generated by a number of coaxially stacked helical domains connected by local and long-range contacts. This flat surface facilitates binding and cleavage of precursor tRNA substrates. For review see [4].

[edit] In archaea

Further information: Archaeal RNase P

In archaea, RNase P ribonucleoproteins consist of 4-5 protein subunits that are associated with RNA. As revealed by in vitro reconstitution experiments these protein subunits are individually dispensable for tRNA processing that is essentially mediated by the RNA component [6], [7], [8]. The structures of protein subunits of archaeal RNase P have been resolved by x-ray crystallography and NMR, thus revealing new protein domains and folding fundamental for function.

It has recently been argued that the archaebacteriium Nanoarchaeum equitans does not possess RNase P. Computational and experimental studies failed to find evidence for its existence. In this organism the tRNA promoter is close to the tRNA gene and it is thought that transcription starts at the first base of the tRNA thus removing the requirement for RNase P. [9]

[edit] In eukaryotes

Further information: Nuclear RNase P

In eukaryotes, such as humans and yeast, RNase P consists of an RNA chain that is structurally similar to that found in bacteria [10] as well as nine to ten associated proteins (as opposed to the single bacterial RNase P protein, C5) [2], [11] . Five of these protein subunits exhibit homology to archaeal counterparts. These protein subunits of RNase P are shared with RNase MRP [11], [12], [13], a catalytic ribonucleoprotein involved in processing of ribosomal RNA in the nucleolus [14]. RNase P RNA from eukaryotes was only recently demonstrated to be a ribozyme [15]. Accordingly, the numerous protein subunits of eucaryal RNase P have a minor contribution to tRNA processing per se [16], while they seem to be essential for the function of RNase P and RNase MRP in other biological settings, such as gene transcription and the cell cycle [3], [17].

[edit] References

  1. ^ a b Guerrier-Takada C, Gardiner K, Marsh T, Pace N, Altman S (1983). "The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme". Cell 35 (3 Pt 2): 849–57. PMID 6197186. 
  2. ^ a b Jarrous N, Reiner R (2007). "Human RNase P: a tRNA-processing enzyme and transcription factor". Nucleic Acids Res. 35 (11): 3519–24. doi:10.1093/nar/gkm071. PMID 17483522. 
  3. ^ a b Reiner R, Ben-Asouli Y, Krilovetzky I, Jarrous N (2006). "A role for the catalytic ribonucleoprotein RNase P in RNA polymerase III transcription". Genes Dev. 20 (12): 1621–35. doi:10.1101/gad.386706. PMID 16778078. 
  4. ^ a b Evans D, Marquez SM, Pace NR (2006). "RNase P: interface of the RNA and protein worlds". Trends Biochem. Sci. 31 (6): 333–41. doi:10.1016/j.tibs.2006.04.007. PMID 16679018. 
  5. ^ Tsai HY, Masquida B, Biswas R, Westhof E, Gopalan V (2003). "Molecular modeling of the three-dimensional structure of the bacterial RNase P holoenzyme". J. Mol. Biol. 325 (4): 661–75. PMID 12507471. 
  6. ^ Hall TA, Brown JW (2002). "Archaeal RNase P has multiple protein subunits homologous to eukaryotic nuclear RNase P proteins". RNA 8 (3): 296–306. PMID 12003490. 
  7. ^ Fukuhara H, Kifusa M, Watanabe M, Terada A, Honda T, Numata T, Kakuta Y, Kimura M (2006). "A fifth protein subunit Ph1496p elevates the optimum temperature for the ribonuclease P activity from Pyrococcus horikoshii OT3". Biochem. Biophys. Res. Commun. 343 (3): 956–64. doi:10.1016/j.bbrc.2006.02.192. PMID 16574071. 
  8. ^ Tsai HY, Pulukkunat DK, Woznick WK, Gopalan V (2006). "Functional reconstitution and characterization of Pyrococcus furiosus RNase P". Proc. Natl. Acad. Sci. U.S.A. 103 (44): 16147–52. doi:10.1073/pnas.0608000103. PMID 17053064. 
  9. ^ Randau L, Schröder I, Söll D (May 2008). "Life without RNase P". Nature 453 (7191): 120–3. doi:10.1038/nature06833. PMID 18451863. 
  10. ^ Marquez SM, Chen JL, Evans D, Pace NR (2006). "Structure and function of eukaryotic Ribonuclease P RNA". Mol. Cell 24 (3): 445–56. doi:10.1016/j.molcel.2006.09.011. PMID 17081993. 
  11. ^ a b Chamberlain JR, Lee Y, Lane WS, Engelke DR (1998). "Purification and characterization of the nuclear RNase P holoenzyme complex reveals extensive subunit overlap with RNase MRP". Genes Dev. 12 (11): 1678–90. PMID 9620854. 
  12. ^ Salinas K, Wierzbicki S, Zhou L, Schmitt ME (2005). "Characterization and purification of Saccharomyces cerevisiae RNase MRP reveals a new unique protein component". J. Biol. Chem. 280 (12): 11352–60. doi:10.1074/jbc.M409568200. PMID 15637077. 
  13. ^ Welting TJ, Kikkert BJ, van Venrooij WJ, Pruijn GJ (2006). "Differential association of protein subunits with the human RNase MRP and RNase P complexes". RNA 12 (7): 1373–82. doi:10.1261/rna.2293906. PMID 16723659. 
  14. ^ Clayton DA (2001). "A big development for a small RNA". Nature 410 (6824): 29, 31. doi:10.1038/35065191. PMID 11242026. 
  15. ^ Kikovska E, Svärd SG, Kirsebom LA (2007). "Eukaryotic RNase P RNA mediates cleavage in the absence of protein". Proc. Natl. Acad. Sci. U.S.A. 104 (7): 2062–7. doi:10.1073/pnas.0607326104. PMID 17284611. 
  16. ^ Willkomm DK, Hartmann RK (2007). "An important piece of the RNase P jigsaw solved". Trends Biochem. Sci. 32 (6): 247–50. doi:10.1016/j.tibs.2007.04.005. PMID 17485211. 
  17. ^ Gill T, Cai T, Aulds J, Wierzbicki S, Schmitt ME (2004). "RNase MRP cleaves the CLB2 mRNA to promote cell cycle progression: novel method of mRNA degradation". Mol. Cell. Biol. 24 (3): 945–53. PMID 14729943. 

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Hydrolase, esterase: nucleases (EC 3.1.11 - 3.1.31) - includes deoxyribonuclease and ribonuclease
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