Ribonuclease P

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(Redirected from
RNase P
)
Crystal structure of a bacterial ribonuclease P holoenzyme in complex with tRNA (yellow), showing metal ions involved in catalysis (pink spheres), PDB: 3Q1R​
Bacterial RNase P class A
GO
GO:0008033 GO:0004526 GO:0030680
SOSO:0000386
PDB structuresPDBe
Bacterial RNase P class B
GO
GO:0008033 GO:0004526 GO:0030680
SOSO:0000386
PDB structuresPDBe
Archaeal RNase P
GO
GO:0008033 GO:0004526 GO:0030680
SOSO:0000386
PDB structuresPDBe
Archaeal RNase P class T
Identifiers
SymbolRNaseP-T
GO
GO:0008033 GO:0004526 GO:0030680
SOSO:0000386
PDB structuresPDBe

Ribonuclease P (

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 Sidney Altman and Thomas Cech the Nobel Prize in Chemistry in 1989: in the 1970s, 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. 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 RNAs, 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.

In Bacteria

Bacterial 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 a bacterial RNase P holoenzyme with tRNA has been recently resolved, showing how the large, coaxially stacked helical domains of the RNase P RNA engage in shape selective recognition of the pre-tRNA target. This crystal structure confirms earlier models of substrate recognition and catalysis, identifies the location of the active site, and shows how the protein component increases RNase P functionality.[6][7]

Bacterial RNase P class A and B

Ribonuclease P (RNase P) is a ubiquitous endoribonuclease, found in archaea, bacteria and eukarya as well as chloroplasts and mitochondria. Its best characterised activity is the generation of mature 5'-ends of tRNAs by cleaving the 5'-leader elements of precursor-tRNAs. Cellular RNase Ps are

ribonucleoproteins
(RNP). RNA from bacterial RNase Ps retains its catalytic activity in the absence of the protein subunit, i.e. it is a ribozyme. Isolated eukaryotic and archaeal RNase P RNA has not been shown to retain its catalytic function, but is still essential for the catalytic activity of the holoenzyme. Although the archaeal and eukaryotic holoenzymes have a much greater protein content than the eubacterial ones, the RNA cores from all the three lineages are homologous—helices corresponding to P1, P2, P3, P4, and P10/11 are common to all cellular RNase P RNAs. Yet, there is considerable sequence variation, particularly among the eukaryotic RNAs.

In Archaea

In

NMR
, thus revealing new protein domains and folding fundamental for function.

Using comparative genomics and improved computational methods, a radically minimized form of the RNase P RNA, dubbed "Type T", has been found in all complete genomes in the crenarchaeal phylogenetic family Thermoproteaceae, including species in the genera Pyrobaculum, Caldivirga and Vulcanisaeta.[11] All retain a conventional catalytic domain, but lack a recognizable specificity domain. 5′ tRNA processing activity of the RNA alone was experimentally confirmed. The Pyrobaculum and Caldivirga RNase P RNAs are the smallest naturally occurring form yet discovered to function as trans-acting ribozymes.[11] Loss of the specificity domain in these RNAs suggests potential altered substrate specificity.

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.[12]

In eukaryotes

Further information: Nuclear RNase P

In

eukaryotes, such as humans and yeast,[13] most RNase P consists of an RNA chain that is structurally similar to that found in bacteria [14] as well as nine to ten associated proteins (as opposed to the single bacterial RNase P protein, C5).[2][15] Five of these protein subunits exhibit homology to archaeal counterparts. These protein subunits of RNase P are shared with RNase MRP,[15][16][17] a catalytic ribonucleoprotein involved in processing of ribosomal RNA in the nucleolus.[18] RNase P from eukaryotes was only recently demonstrated to be a ribozyme.[19] Accordingly, the numerous protein subunits of eucaryal RNase P have a minor contribution to tRNA processing per se,[20] 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][21] Despite the bacterial origins of mitochondria and chloroplasts, plastids from higher animals and plants do not appear to contain an RNA-based RNase P. It has been shown that human mitochondrial RNase P is a protein and does not contain RNA.[22] Spinach chloroplast RNase P has also been shown to function without an RNA subunit.[23]

Subunits and functions of human RNase P [2]
Subunit Function/interaction (in tRNA processing)
RPP14 RNA binding
RPP20 ATPase, helicase/Hsp27, SMN, Rpp25
RPP21 RNA binding, activityg/Rpp29
RPP25 RNA binding/Rpp20
RPP29 tRNA binding, activity/Rpp21
RPP30 RNA binding, activity/Pop5
RPP38 RNA binding, activity
RPP40
hPop1
hPop5 RNA binding, activity/Rpp30
H1 RNA Activity/Rpp21, Rpp29, Rpp30, Rpp38

Therapies using RNase P

RNase P is now being studied as a potential therapy for diseases such as

tRNA.[26] These structures allow RNase P to recognize the EGS and cleave the target mRNA. EGS therapies have shown to be effective in culture and in live mice.[29]

References

  1. ^
    S2CID 39111511
    .
  2. ^
    PMID 17483522
    .
  3. ^
    PMID 16778078
    .
  4. PMID 16679018
    .
  5. PMID 12507471. Archived from the original
    (PDF) on 2008-10-31. Retrieved 2019-09-24.
  6. PMID 21076397
    .
  7. PMID 21803972
    .
  8. PMID 12003490
    .
  9. PMID 16574071
    .
  10. PMID 17053064
    .
  11. ^
    PMID 21135215
    .
  12. S2CID 3103527
    .
  13. ^ Randall Munroe rephrased this as “You know, eukaryotes—like sourdough starter or Conan O’Brien.” (Munroe, Randall (30 September 2022). "4:25 PM". Twitter. Retrieved 1 October 2022.)
  14. PMID 17081993
    .
  15. ^
    PMID 9620854
    .
  16. PMID 15637077
    .
  17. PMID 16723659
    .
  18. PMID 11242026
    .
  19. PMID 17284611
    .
  20. PMID 17485211
    .
  21. PMID 14729943
    .
  22. S2CID 476465
    .
  23. PMID 10786845
    .
  24. ^
    S2CID 19365318
    .
  25. PMID 12361758
    .
  26. ^
    PMID 19707312
    .
  27. PMID 23300569
    .
  28. PMID 10648380
    .
  29. PMID 23727592
    .

Further reading

External links
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