Potent degradation of neuronal miRNAs induced by highly complementary targets

EMBO Reports
Manuel de la MataHelge Großhans

Abstract

MicroRNAs (miRNAs) regulate target mRNAs by silencing them. Reciprocally, however, target mRNAs can also modulate miRNA stability. Here, we uncover a remarkable efficacy of target RNA-directed miRNA degradation (TDMD) in rodent primary neurons. Coincident with degradation, and while still bound to Argonaute, targeted miRNAs are 3' terminally tailed and trimmed. Absolute quantification of both miRNAs and their decay-inducing targets suggests that neuronal TDMD is multiple turnover and does not involve co-degradation of the target but rather competes with miRNA-mediated decay of the target. Moreover, mRNA silencing, but not TDMD, relies on cooperativity among multiple target sites to reach high efficacy. This knowledge can be harnessed for effective depletion of abundant miRNAs. Our findings bring insight into a potent miRNA degradation pathway in primary neurons, whose TDMD activity greatly surpasses that of non-neuronal cells and established cell lines. Thus, TDMD may be particularly relevant for miRNA regulation in the nervous system.

References

Feb 1, 1985·The Journal of Cell Biology·M E Hatten
Dec 26, 2001·Nucleic Acids Research·Ron EdgarAlex E Lash
Dec 31, 2003·Cell·Benjamin P LewisChristopher B Burge
Nov 6, 2004·Science·Binzhang Shen, Howard M Goodman
Feb 1, 2005·Science·Ben ChihPeter Scheiffele
Nov 2, 2005·Proceedings of the National Academy of Sciences of the United States of America·Ngan VoSoren Impey
Nov 26, 2005·Science·Kyle Kai-How FarhDavid P Bartel
Jan 6, 2007·Science·Hun-Way HwangJoshua T Mendell
Mar 29, 2007·Nucleic Acids Research·Pål SaetromJohn J Rossi
Jul 7, 2007·Molecular Cell·Andrew GrimsonDavid P Bartel
Nov 7, 2007·Journal of Neuroscience Methods·Sergio GascónFrancisco G Scholl
Sep 13, 2008·Science·Vanitharani Ramachandran, Xuemei Chen
Jun 3, 2009·Genes & Development·David GatfieldUeli Schibler
Aug 25, 2009·Nature Cell Biology·Matthew R JonesJoseph P Mizgerd
Oct 7, 2009·Cell·Josien C van WolfswinkelRené F Ketting
Nov 6, 2009·Nature Reviews. Neuroscience·Gerhard Schratt
Jun 19, 2010·Science·Stefan L AmeresPhillip D Zamore
Jun 19, 2010·Science·Demián CazallaJoan A Steitz
Jul 28, 2010·Nature Reviews. Genetics·Jacek KrolWitold Filipowicz
Nov 26, 2010·Molecular Cell·Edlyn WuThomas F Duchaine
Mar 1, 2011·Current Biology : CB·Alessia BaccariniBrian D Brown
Dec 21, 2011·Proceedings of the National Academy of Sciences of the United States of America·Valentina LibriAmy H Buck
Jul 31, 2012·Nucleic Acids Research·Anne DueckGunter Meister
Aug 14, 2012·Neuron·Elizabeth McNeill, David Van Vactor
Mar 1, 2013·Nature·Thomas B HansenJørgen Kjems
Mar 1, 2013·Nature·Sebastian MemczakNikolaus Rajewsky
Jun 27, 2013·Nature Reviews. Molecular Cell Biology·Stefan L Ameres, Phillip D Zamore
Nov 28, 2013·Nucleic Acids Research·Ana Kozomara, Sam Griffiths-Jones

❮ Previous
Next ❯

Citations

Jan 19, 2016·Nature Structural & Molecular Biology·Hannes RichterHelge Großhans
Feb 3, 2016·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Jennifer Y Tan, Ana C Marques
Jan 27, 2016·Nucleic Acids Research·Gabrielle HaasSébastien Pfeffer
Dec 18, 2015·Nucleic Acids Research·Károly FátyolJózsef Burgyán
Jul 23, 2016·Nature Communications·Mainak Bose, Suvendra N Bhattacharyya
Jan 26, 2017·Nucleic Acids Research·June Hyun ParkChanseok Shin
May 12, 2018·FEBS Letters·Igor Ulitsky
Aug 16, 2018·Wiley Interdisciplinary Reviews. RNA·Benjamin P Towler, Sarah F Newbury
Feb 28, 2018·Nature Structural & Molecular Biology·Angelo BitettiAlena Shkumatava
Mar 7, 2018·Nature Structural & Molecular Biology·Manuel de la Mata, Helge Großhans
Jul 13, 2016·EMBO Reports·Kamalika MukherjeeSuvendra N Bhattacharyya
Nov 29, 2015·Biochemical Society Transactions·Benjamin P TowlerSarah F Newbury
Feb 29, 2020·Bioscience, Biotechnology, and Biochemistry·Akira TachibanaAiko Yamamoto
Feb 6, 2020·Cold Spring Harbor Symposia on Quantitative Biology·Paulina PawlicaJoan A Steitz
Aug 14, 2020·American Journal of Physiology. Cell Physiology·Chun K Kim, Toni R Pak
Sep 22, 2020·Wiley Interdisciplinary Reviews. RNA·Jeffrey C MedleyAnna Y Zinovyeva
Oct 7, 2017·Wiley Interdisciplinary Reviews. RNA·Caroline De AlmeidaDominique Gagliardi
Oct 20, 2018·Frontiers in Genetics·Erika GirardiSébastien Pfeffer
Jun 4, 2019·Frontiers in Pharmacology·Svetlana Miroshnichenko, Olga Patutina
Aug 10, 2019·Frontiers in Cellular Neuroscience·Simona Federica SpampinatoMaria Angela Sortino
Oct 1, 2020·International Journal of Molecular Sciences·Dylan J Kiltschewskij, Murray J Cairns
Oct 20, 2018·Frontiers in Genetics·Federico Fuchs WightmanManuel de la Mata
Apr 12, 2019·Frontiers in Plant Science·Junli WangGuodong Ren
Sep 15, 2019·Genome Research·Elena R Kingston, David P Bartel
Nov 7, 2018·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Dagmar Zigáčková, Štěpánka Vaňáčová
Jun 26, 2020·Frontiers in Cell and Developmental Biology·Philipp J Dexheimer, Luisa Cochella
Aug 16, 2018·Nature Reviews. Molecular Cell Biology·Luca F R Gebert, Ian J MacRae
Oct 16, 2019·Frontiers in Oncology·Roberta RoncaratiMassimo Negrini
Sep 29, 2020·PeerJ·Stepan NersisyanAlexander Tonevitsky
Jun 26, 2020·Proceedings of the National Academy of Sciences of the United States of America·Morten T VenøDavid C Henshall

❮ 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.