Nejvíce citovaný článek - PubMed ID 11032819
Most eukaryotic RNAs are posttranscriptionally modified. The majority of modifications promote RNA maturation, others may regulate function and stability. The 3' terminal non-templated oligouridylation is a widespread modification affecting many cellular RNAs at some stage of their life cycle. It has diverse roles in RNA metabolism. The most prevalent is the regulation of stability and quality control. On the cellular and organismal level, it plays a critical role in a number of pathways, such as cell cycle regulation, cell death, development or viral infection. Defects in uridylation have been linked to several diseases. This review summarizes the current knowledge about the role of the 3' terminal oligo(U)-tailing in biology of various RNAs in eukaryotes and describes key factors involved in these pathways.This article is part of the theme issue '5' and 3' modifications controlling RNA degradation'.
- Klíčová slova
- RNA degradation, RNA modification, RNA processing, RNA surveillance, RNA uridylation, tutase,
- MeSH
- Eukaryota MeSH
- eukaryotické buňky fyziologie MeSH
- lidé MeSH
- RNA metabolismus MeSH
- úpravy 3' konce RNA * MeSH
- uridin metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- RNA MeSH
- uridin MeSH
The mitochondrial RNA binding complex 1 (MRB1) is a recently discovered complex of proteins associated with the TbRGG1 and TbRGG2 proteins in Trypanosoma brucei. Based on the phenotype caused by down-regulation of these two proteins, it was proposed to play an unspecified role in RNA editing. RNAi silencing of three newly characterized protein subunits, guide RNA associated proteins (GAPs) 1 and 2 as well as a predicted DExD/H-box RNA helicase, show they are essential for cell growth in the procyclic stage. Furthermore, their down-regulation leads to inhibition of editing in only those mRNAs for which minicircle-encoded guide (g) RNAs are required. However, editing remains unaffected when the maxicircle-encoded cis-acting gRNA is employed. Interestingly, all three proteins are necessary for the expression of the minicircle-encoded gRNAs. Moreover, down-regulation of a fourth assayed putative MRB1 subunit, Nudix hydrolase, does not appear to destabilize gRNAs, and down-regulation of this protein has a general impact on the stability of maxicircle-encoded RNAs. GAP1 and 2 are also essential for the survival of the bloodstream stage, in which the gRNAs become eliminated upon depletion of either protein. Immunolocalization revealed that GAP1 and 2 are concentrated into discrete spots along the mitochondrion, usually localized in the proximity of the kinetoplast. Finally, we demonstrate that the same mtRNA polymerase known to transcribe the maxicircle mRNAs may also have a role in expression of the minicircle-encoded gRNAs.
- MeSH
- DEAD-box RNA-helikasy metabolismus MeSH
- DNA řízené RNA-polymerasy metabolismus MeSH
- guide RNA, Kinetoplastida genetika MeSH
- mitochondriální proteiny metabolismus MeSH
- NUDIX hydrolasy MeSH
- proteiny vázající RNA metabolismus MeSH
- protozoální proteiny metabolismus MeSH
- pyrofosfatasy metabolismus MeSH
- RNA mitochondriální MeSH
- RNA protozoální genetika MeSH
- RNA genetika MeSH
- Trypanosoma brucei brucei genetika růst a vývoj MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- DEAD-box RNA-helikasy MeSH
- DNA řízené RNA-polymerasy MeSH
- guide RNA, Kinetoplastida MeSH
- mitochondriální proteiny MeSH
- proteiny vázající RNA MeSH
- protozoální proteiny MeSH
- pyrofosfatasy MeSH
- RNA mitochondriální MeSH
- RNA protozoální MeSH
- RNA MeSH
Kinetoplastids are flagellated protozoans, whose members include the pathogens Trypanosoma brucei, T. cruzi and Leishmania species, that are considered among the earliest diverging eukaryotes with a mitochondrion. This organelle has become famous because of its many unusual properties, which are unique to the order Kinetoplastida, including an extensive kinetoplast DNA network and U-insertion/deletion type RNA editing of its mitochondrial transcripts. In the last decade, considerable progress has been made in elucidating the complex machinery of RNA editing. Moreover, our understanding of the structure and replication of kinetoplast DNA has also dramatically improved. Much less however, is known, about the developmental regulation of RNA editing, its integration with other RNA maturation processes, stability of mitochondrial mRNAs, or evolution of the editing process itself. Yet the profusion of genomic data recently made available by sequencing consortia, in combination with methods of reverse genetics, hold promise in understanding the complexity of this exciting organelle, knowledge of which may enable us to fight these often medically important protozoans.
- MeSH
- editace RNA MeSH
- exprese genu MeSH
- genetická transkripce MeSH
- genom protozoální * MeSH
- Kinetoplastida genetika MeSH
- kinetoplastová DNA chemie MeSH
- messenger RNA metabolismus MeSH
- mitochondriální geny * MeSH
- mitochondrie genetika MeSH
- RNA protozoální metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- kinetoplastová DNA MeSH
- messenger RNA MeSH
- RNA protozoální MeSH