Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/10/11 19:33:40」(JST)

wiki en

Guide RNAs (aka gRNA) are the RNAs that guide the insertion or deletion of uridine residues into mitochondrial mRNAs in kinetoplastid protists in a process known as RNA editing.

Overview of gRNA-directed editing

Trypanosomatid protists and other kinetoplastids have a novel post-transcriptional mitochondrial RNA modification process known as "RNA editing". The mitochondrial genome in these cells consists of 20-50 maxicircles that encode genes and "cryptogenes" (and some gRNAs) and 10-20,000 minicircles that encode gRNAs. All of these molecules are catenated into a giant network of DNA that is situated at the base of the flagellum in the inner compartment of the single mitochondrion.

A majority of the maxicircle transcripts can not be translated into proteins due to multiple frameshifts in the sequences. These frameshifts are corrected after transcription by the insertion and deletion of uridine residues at precise sites which create an open reading frame that is translated into a mitochondrial protein homologous to mitochondrial proteins from other cells. The insertions and deletions are mediated by short guide RNA (gRNAs) which encode the editing information in the form of complementary sequences (allowing GU as well as GC base pairs). The gRNAs are transcribed from both the maxicircles and the minicircles.

The presence of two genomes in the mitochondrion, one of which contains sequence information that corrects errors in the other genome, is novel. Editing proceeds generally 3' to 5' on the mRNA. The initial editing event occurs when a gRNA forms an RNA duplex with a complementary mRNA sequence just downstream of the editing site. This then recruits a number of ribonucleoprotein complexes that direct the precise insertions and deletions of uridine residues, thereby extending the duplex upstream. The adjacent upstream editing site is then modified in the same manner. A single gRNA usually encodes the information for several editing sites (an editing "block"), the editing of which produces a complete gRNA/mRNA duplex.

In the case of "pan-edited" mRNAs, the duplex unwinds and another gRNA then forms a duplex with the edited mRNA sequence and initiates another round of editing. The overlapping gRNAs form an editing "domain". In some genes there are multiple editing domains. The extent of editing for any particular gene varies between trypanosomatid species. The variation consists of the loss of editing at the 3' side, probably due to the loss of minicircle sequence classes that encode specific gRNAs. A retroposition model has been proposed to account for the partial, and in some cases, complete, loss of editing in evolution. Loss of editing is lethal in most cases, although losses have been seen in old laboratory strains. The maintenance of editing over the long evolutionary history of these ancient protists implies the presence of a selective advantage, the exact nature of which is still uncertain.

It is not clear why trypanosomatids utilize such an elaborate mechanism to produce mRNAs. It may have originated in the early mitochondrion of the ancestor of the kintoplastid protist lineage, since it is present in the bodonids which are ancestral to the trypanosomatids, and may not be present in the euglenoids, which branched from the same common ancestor as the kinetoplastids.

In the protozoan Leishmania tarentolae, 12 of the 18 mitochondrial genes are edited using this process. One such gene is Cyb.^[1] The mRNA is actually edited twice in succession. For the first edit, the relevant sequence on the mRNA is

mRNA 5' AAAGAAAAGGCUUUAACUUCAGGUUGU 3'

The 3' end is used to anchor the gRNA (gCyb-I gRNA in this case) by basepairing (some G/U pairs are used). The 5' end does not exactly match and one of three specific endonucleases cleaves the mRNA at the mismatch site.

gRNA 3' AAUAAUAAAUUUUUAAAUAUAAUAGAAAAUUGAAGUUCAGUA 5'
mRNA 5'   A  A   AGAAA   A G  G C UUUAACUUCAGGUUGU 3'

The mRNA is now "repaired" by adding U's at each editing site in succession, giving the sequence

gRNA 3' AAUAAUAAAUUUUUAAAUAUAAUAGAAAAUUGAAGUUCAGUA 5'
mRNA 5' UUAUUAUUUAGAAAUUUAUGUUGUCUUUUAACUUCAGGUUGU 3'

This particular gene has two overlapping gRNA editing sites. The 5' end of this section is the 3' anchor for another gRNA (gCyb-II gRNA).

References

^ Simpson, Larry (2009-08-12). "Uridine insertion/deletion RNA editing". UCLA. http://dna.kdna.ucla.edu/trypanosome/index.html. Retrieved 2006-05-19.

English Journal

PIWIL1 Is Expressed in the Canine Testis, Increases with Sexual Maturity, and Binds Small RNAs.

Stalker L1, Russell SJ1, Co C1, Foster RA2, LaMarre J3.
Biology of reproduction.Biol Reprod.2016 Dec;94(1):17. doi: 10.1095/biolreprod.115.131854. Epub 2015 Dec 9.
Spermatogenesis is a highly regulated process leading to the development of functional spermatozoa through meiotic division and subsequent maturation. Recent studies have suggested that a novel class of Argonaute proteins, known as the PIWI clade, plays important roles in multiple stages of spermato
PMID 26658707

Transcriptional induction of protein kinase C delta by p53 tumor suppressor in the apoptotic response to DNA damage.

Dashzeveg N1, Yogosawa S1, Yoshida K2.
Cancer letters.Cancer Lett.2016 Apr 28;374(1):167-74. doi: 10.1016/j.canlet.2016.02.012. Epub 2016 Feb 13.
Genetic alterations and aberrant gene expression trigger malignant tumors. Tumor suppressor p53 is the most altered gene in human cancers. p53 induces apoptosis by promoting pro-apoptotic genes in response to DNA damage. Protein kinase C delta (PKCδ) also induces apoptosis via various mechanisms in
PMID 26884258

Chemical modifications in the seed region of miRNAs 221/222 increase the silencing performances in gastrointestinal stromal tumor cells.

Durso M1, Gaglione M2, Piras L3, Mercurio ME2, Terreri S1, Olivieri M1, Marinelli L4, Novellino E4, Incoronato M5, Grieco P4, Orsini G6, Tonon G6, Messere A7, Cimmino A8.
European journal of medicinal chemistry.Eur J Med Chem.2016 Mar 23;111:15-25. doi: 10.1016/j.ejmech.2016.01.047. Epub 2016 Jan 27.
Most GastroIntestinal Stromal Tumors (GISTs) are characterized by KIT gene overexpression, which in turn is regulated by levels of microRNA 221 and microRNA 222. GISTs can also be distinguished by their miRNAs expression profile in which miRNAs 221/222 result reduced in comparison with GI normal tis
PMID 26854374

Japanese Journal

進行再発消化器癌における腫瘍内DPDおよびTSm-RNA量の検討

近藤建,片岡政人,木下水信,坪井賢治,下山理史,大谷聡,三浦啓多,市原透,陳鶴祥,堀澤増雅
日本外科学会雑誌 103(臨時増刊), 480, 2002-03-10
NAID 110003950961

Mitochondrial Proteins Interacting with Guide RNAs (RESEARCH FACILITY OF NUCLEIC ACIDS)

ICR annual report 5, 58-59, 1999-03
… The aim of this study was to identify mitochondrial proteins that are in direct physical contacts with gRNA molecules, thereby possibly responsible for the RNA editing reaction. … One of them probably contacts with 3’ poly(U)n tails of the gRNA molecules because the binding of the protein was sensitive to the presence of oligo (U)n. …
NAID 120000885623