Diverse endonucleolytic cleavage sites in the mammalian transcriptome depend upon microRNAs, Drosha, and additional nucleases.

Molecular Cell
Fedor V KarginovGregory J Hannon

Abstract

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.

References

Jun 5, 2002·Genome Research·W James KentDavid Haussler
Apr 14, 2004·Genome Research·Ewan BirneyMichele Clamp
Apr 24, 2004·Genes & Development·Javier Martinez, Thomas Tuschl
Apr 24, 2004·Science·Soraya YektaDavid P Bartel
May 4, 2004·Current Biology : CB·Dianne S SchwarzPhillip D Zamore
Jun 1, 2004·Nature Structural & Molecular Biology·Benjamin Haley, Phillip D Zamore
Jul 31, 2004·Science·Jidong LiuGregory J Hannon
Jun 1, 2005·Trends in Genetics : TIG·Neil R Smalheiser, Vetle I Torvik
Feb 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Alysha M HeimbergKevin J Peterson
May 13, 2008·Current Biology : CB·Charles Addo-QuayeMichael J Axtell
Jun 11, 2008·Nature Biotechnology·Marcelo A GermanPamela J Green
Sep 9, 2008·Nucleic Acids Symposium Series·Mikiko C Siomi, Haruhiko Siomi
Nov 26, 2008·Molecular Cell·Christine EnderGunter Meister
Dec 9, 2008·Nature Structural & Molecular Biology·Andrea B EberleTorben Heick Jensen
Feb 19, 2009·Molecular and Cellular Biology·Yuichi OtsukaDaniel R Schoenberg
Feb 26, 2009·Cell·Richard W Carthew, Erik J Sontheimer
Feb 26, 2009·Cell·Olivier Voinnet
Sep 9, 2009·Bioinformatics·Andrew D SmithMichael Q Zhang

❮ Previous
Next ❯

Citations

Jun 19, 2012·Nature Neuroscience·Philip KnucklesVerdon Taylor
Mar 7, 2012·Nature Reviews. Genetics·Daniel R Schoenberg, Lynne E Maquat
Jun 27, 2013·Nature Reviews. Molecular Cell Biology·Stefan L Ameres, Phillip D Zamore
May 15, 2012·Nature Structural & Molecular Biology·Omer BaradEran Hornstein
Jul 17, 2012·Nature Structural & Molecular Biology·Sara MaciasJavier F Cáceres
Sep 3, 2013·Nature Structural & Molecular Biology·Sara R HerasJavier F Cáceres
Jul 4, 2012·Proceedings of the National Academy of Sciences of the United States of America·Yuriko Harigaya, Roy Parker
Nov 16, 2010·Nucleic Acids Research·Tim R MercerJohn S Mattick
Jun 10, 2011·Nucleic Acids Research·Daniel W ThomsonGregory J Goodall
Jun 10, 2011·Nucleic Acids Research·Paulina JackowiakMarek Figlerowicz
Sep 13, 2011·Nucleic Acids Research·Wlodzimierz J KrzyzosiakPiotr Kozlowski
Oct 25, 2013·Open Biology·Timothy M JohansonMark M W Chong
Apr 5, 2012·Genes & Development·Dongmei WangRui Yi
Nov 4, 2010·Genome Research·Tim R MercerJohn S Mattick
Jul 25, 2013·The Plant Cell·Kestrel Rogers, Xuemei Chen
Apr 21, 2011·Human Genomics·Eneritz Agirre, Eduardo Eyras
May 11, 2011·Genome Biology·Michael J AxtellEric C Lai
May 18, 2011·Journal of Cell Science·Rui Yi, Elaine Fuchs
Oct 26, 2012·RNA·Thomas MaurinEric C Lai
Jan 30, 2013·PloS One·Daniel W ThomsonGregory J Goodall
Jan 29, 2014·Cellular and Molecular Life Sciences : CMLS·Anna Stroynowska-CzerwinskaWlodzimierz J Krzyzosiak
Apr 30, 2014·Proceedings of the National Academy of Sciences of the United States of America·Jillian S ShapiroBenjamin R tenOever
Apr 30, 2014·Proceedings of the National Academy of Sciences of the United States of America·Shitao LiMartin E Dorf
Mar 20, 2014·Genome Research·Yehu MoranHervé Seitz
Mar 15, 2013·FEBS Letters·June Hyun ParkChanseok Shin
Dec 30, 2015·International Journal of Molecular Sciences·Patrick ConnertyGyorgy Hutvagner
Oct 30, 2016·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Brock HumphriesChengfeng Yang
May 23, 2013·Journal of Cellular Physiology·Julian C RobertsKehinde Ross
Jun 21, 2011·Biochimica Et Biophysica Acta·Yong FengYan Zeng
Jul 12, 2011·Trends in Genetics : TIG·Alex C Tuck, David Tollervey
Nov 17, 2011·Wiley Interdisciplinary Reviews. RNA·Katsutomo Okamura
Oct 28, 2011·IUBMB Life·Janet H C Yeo, Mark M W Chong
Oct 12, 2012·Annals of the New York Academy of Sciences·Dooyoung Lee, Chanseok Shin

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.