ScienceDaily (June 25, 2010) — One way of regulating protein levels in cells is to shorten the lifespan of messenger RNAs (mRNAs). These are intermediary molecules that are first copied from DNA in the cell's nucleus via a process called transcription and then transported into the cell's body to be translated into protein.
"In addition to revealing the surprising diversity of post-transcriptional events that regulate mRNAs, our work also points to new roles for a family of proteins that mediate RNA interference or RNAi," said CSHL Professor and HHMI Investigator Gregory Hannon, Ph.D., who led the team.
In RNAi, tiny bits of RNA that are about 21 "letters" or nucleotides long latch on to longer messenger RNA strands at regions where their nucleotide sequences are complementary. The tiny RNAs, called microRNAs, serve as guides to a family of proteins called Argonautes. The binding of the microRNA-Argonaute complex to its mRNA target triggers its destruction.
In mammals, this destruction has, until now, mostly been attributed to the activation of cellular pathways that destabilize the mRNA molecule, causing it to decay. By using a method that combines computational predictions with experimental testing, Hannon's group has now detected other modes of mRNA destruction that involve cleavage of mRNAs by various catalytic, or slicing, enzymes.
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Molecular Cell, Volume 38, Issue 6, 781-788, 25 June 2010 | Copyright © 2010 Elsevier Inc. All rights reserved. | 10.1016/j.molcel.2010.06.001
Diverse Endonucleolytic Cleavage Sites in the Mammalian Transcriptome Depend upon MicroRNAs, Drosha, and Additional Nucleases
Diverse Endonucleolytic Cleavage Sites in the Mammalian Transcriptome Depend upon MicroRNAs, Drosha, and Additional Nucleases
Fedor V. Karginov,Sihem Cheloufi,Mark M.W. Chong,Alexander Stark,Andrew D. Smith,Gregory J. Hannon
Transcriptome-wide RACE identifies sites of endonucleolytic cleavage in mRNAs
Ago2 catalyzes numerous miRNA-guided mRNA cleavages
Drosha appears to have many mRNA substrates, which it may cleave directly
Ago2- and Drosha-independent cleavages imply involvement of additional nucleases
Summary
The life span of a mammalian mRNA is determined, in part, by the binding of regulatory proteins and small RNA-guided complexes. The conserved endonuclease activity of Argonaute2 requires extensive complementarity between a small RNA and its target and is not used by animal microRNAs, which pair with their targets imperfectly. Here we investigate the endonucleolytic function of Ago2 and other nucleases by transcriptome-wide profiling of mRNA cleavage products retaining 5′ phosphate groups in mouse embryonic stem cells (mESCs). We detect a prominent signature of Ago2-dependent cleavage events and validate several such targets. Unexpectedly, a broader class of Ago2-independent cleavage sites is also observed, indicating participation of additional nucleases in site-specific mRNA cleavage. Within this class, we identify a cohort of Drosha-dependent mRNA cleavage events that functionally regulate mRNA levels in mESCs, including one in the Dgcr8 mRNA. Together, these results highlight the underappreciated role of endonucleolytic cleavage in controlling mRNA fates in mammals.
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NOTA DESTE BLOGGER:
Quanto mais a ciência avançar, nós veremos mais e mais complexidade nas coisas vivas que uma teoria do século 19, epistemicamente moribunda no século 20, não consegue explicar essa complexidade no século 21.
Que venga la nueva teoría de evolución, a SÍNTESE EVOLUTIVA AMPLIADA que, por essa e outras descobertas científicas, não pode ser selecionista. A não ser que prevaleça a ideologia do materialismo filosófico que posa como se fosse ciência...
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