Microprocessor complex: Difference between revisions
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{{About|the protein complex|the computer processor|Microprocessor}} |
{{About|the protein complex|the computer processor|Microprocessor}} |
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The '''Microprocessor complex''' is a [[protein complex]] involved in the |
The '''Microprocessor complex''' is a [[protein complex]] involved in the early stages of processing [[microRNA]] (miRNA) in animal cells.<ref name=gregory /><ref name=denli /> The complex is minimally composed of the [[ribonuclease]] enzyme [[Drosha]] and the [[RNA-binding protein]] DCGR8 (also known as Pasha) and cleaves primary miRNA [[substrate (chemistry)|substrate]]s to pre-miRNA in the [[cell nucleus]].<ref name=siomi /><ref name=wilson /><ref name=macias /> Neither protein has a [[homology (biology)|homolog]] in plant cells, where the first step in miRNA processing is executed by a different ribonuclease, [[DCL1]].<ref name=ha /><ref name=axtell /> |
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==Components== |
==Components== |
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<ref name="siomi">{{cite journal|last1=Siomi|first1=H|last2=Siomi|first2=MC|title=Posttranscriptional regulation of microRNA biogenesis in animals.|journal=Molecular cell|date=14 May 2010|volume=38|issue=3|pages=323-32|pmid=20471939}}</ref> |
<ref name="siomi">{{cite journal|last1=Siomi|first1=H|last2=Siomi|first2=MC|title=Posttranscriptional regulation of microRNA biogenesis in animals.|journal=Molecular cell|date=14 May 2010|volume=38|issue=3|pages=323-32|pmid=20471939}}</ref> |
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<ref name="macias">{{cite journal|last1=Macias|first1=S|last2=Cordiner|first2=RA|last3=Cáceres|first3=JF|title=Cellular functions of the microprocessor.|journal=Biochemical Society transactions|date=August 2013|volume=41|issue=4|pages=838-43|pmid=23863141}}</ref> |
<ref name="macias">{{cite journal|last1=Macias|first1=S|last2=Cordiner|first2=RA|last3=Cáceres|first3=JF|title=Cellular functions of the microprocessor.|journal=Biochemical Society transactions|date=August 2013|volume=41|issue=4|pages=838-43|pmid=23863141}}</ref> |
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<ref name="ha">{{cite journal|last1=Ha|first1=M|last2=Kim|first2=VN|title=Regulation of microRNA biogenesis.|journal=Nature reviews. Molecular cell biology|date=August 2014|volume=15|issue=8|pages=509-24|pmid=25027649}}</ref> |
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<ref name="axtell">{{cite journal|last1=Axtell|first1=MJ|last2=Westholm|first2=JO|last3=Lai|first3=EC|title=Vive la différence: biogenesis and evolution of microRNAs in plants and animals.|journal=Genome biology|date=2011|volume=12|issue=4|pages=221|pmid=21554756}}</ref> |
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Revision as of 20:02, 15 February 2016
The Microprocessor complex is a protein complex involved in the early stages of processing microRNA (miRNA) in animal cells.[1][2] The complex is minimally composed of the ribonuclease enzyme Drosha and the RNA-binding protein DCGR8 (also known as Pasha) and cleaves primary miRNA substrates to pre-miRNA in the cell nucleus.[3][4][5] Neither protein has a homolog in plant cells, where the first step in miRNA processing is executed by a different ribonuclease, DCL1.[6][7]
Components
The Microprocessor complex consists minimally of two proteins: Drosha, a ribonuclease III enzyme; and DGCR8 (also known as Pasha), a double-stranded RNA binding protein.[3][4][5] The stoichiometry of the minimal complex has been experimentally difficult to determine, but has been reported as a heterotrimer of two DCGR8 proteins to one Drosha.[8][9][10]
In addition to the minimal catalytically active Microprocessor components, additional cofactors such as DEAD box RNA helicases and heterogeneous nuclear ribonucleoproteins may be present in the complex to mediate the activity of Drosha.[3]
Function
Located in the cell nucleus, the complex cleaves primary miRNA (pri-miRNA), typically at least 1000 nucleotides long, into precursor miRNA (pre-miRNA) molecules of around 70 nucleotides containing a stem-loop or hairpin structure. Pri-miRNA substrates can be derived either from non-coding RNA genes or from introns. In the latter case, there is evidence that the Microprocessor complex interacts with the spliceosome and that the pri-miRNA processing occurs prior to splicing.[11][4]
DCGR8 recognizes the junctions between hairpin structures and single-stranded RNA and serves to orient Drosha to cleave around 11 nucleotides away from the junctions. Microprocessor cleavage of pri-miRNAs typically occurs co-transcriptionally[12] and leaves a characteristic RNase III single-stranded overhang of 2-3 nucleotides, which serves as a recognition element for the transport protein exportin-5. Pre-miRNAs are exported from the nucleus to the cytoplasm in a RanGTP-dependent manner and are further processed, typically by the endoribonuclease enzyme Dicer.[3][4][5]
Although the large majority of miRNAs undergo processing by Microprocessor, a small number of exceptions called mirtrons have been described; these are very small introns which, after splicing, have the appropriate size and stem-loop structure to serve as a pre-miRNA.[13] The processing pathways for microRNA and for exogenously derived small interfering RNA converge at the point of Dicer processing and are largely identical downstream. Broadly defined, both pathways constitute RNA interference.[4][13]
References
- ^ Gregory, RI; Yan, KP; Amuthan, G; Chendrimada, T; Doratotaj, B; Cooch, N; Shiekhattar, R (11 November 2004). "The Microprocessor complex mediates the genesis of microRNAs". Nature. 432 (7014): 235–40. PMID 15531877.
- ^ Denli, AM; Tops, BB; Plasterk, RH; Ketting, RF; Hannon, GJ (11 November 2004). "Processing of primary microRNAs by the Microprocessor complex". Nature. 432 (7014): 231–5. PMID 15531879.
- ^ a b c d Siomi, H; Siomi, MC (14 May 2010). "Posttranscriptional regulation of microRNA biogenesis in animals". Molecular cell. 38 (3): 323–32. PMID 20471939.
- ^ a b c d e Wilson, RC; Doudna, JA (2013). "Molecular mechanisms of RNA interference". Annual review of biophysics. 42: 217–39. PMID 23654304.
- ^ a b c Macias, S; Cordiner, RA; Cáceres, JF (August 2013). "Cellular functions of the microprocessor". Biochemical Society transactions. 41 (4): 838–43. PMID 23863141.
- ^ Ha, M; Kim, VN (August 2014). "Regulation of microRNA biogenesis". Nature reviews. Molecular cell biology. 15 (8): 509–24. PMID 25027649.
- ^ Axtell, MJ; Westholm, JO; Lai, EC (2011). "Vive la différence: biogenesis and evolution of microRNAs in plants and animals". Genome biology. 12 (4): 221. PMID 21554756.
- ^ Herbert, KM; Sarkar, SK; Mills, M; Delgado De la Herran, HC; Neuman, KC; Steitz, JA (February 2016). "A heterotrimer model of the complete Microprocessor complex revealed by single-molecule subunit counting". RNA (New York, N.Y.). 22 (2): 175–83. PMID 26683315.
- ^ Nguyen, TA; Jo, MH; Choi, YG; Park, J; Kwon, SC; Hohng, S; Kim, VN; Woo, JS (4 June 2015). "Functional Anatomy of the Human Microprocessor". Cell. 161 (6): 1374–87. PMID 26027739.
- ^ Kwon, SC; Nguyen, TA; Choi, YG; Jo, MH; Hohng, S; Kim, VN; Woo, JS (14 January 2016). "Structure of Human DROSHA". Cell. 164 (1–2): 81–90. PMID 26748718.
- ^ Kataoka, N; Fujita, M; Ohno, M (June 2009). "Functional association of the Microprocessor complex with the spliceosome". Molecular and cellular biology. 29 (12): 3243–54. PMID 19349299.
- ^ Morlando, M; Ballarino, M; Gromak, N; Pagano, F; Bozzoni, I; Proudfoot, NJ (September 2008). "Primary microRNA transcripts are processed co-transcriptionally". Nature structural & molecular biology. 15 (9): 902–9. PMID 19172742.
- ^ a b Winter, J; Jung, S; Keller, S; Gregory, RI; Diederichs, S (March 2009). "Many roads to maturity: microRNA biogenesis pathways and their regulation". Nature cell biology. 11 (3): 228–34. PMID 19255566.