Identification of PNG kinase substrates uncovers interactions with the translational repressor TRAL in the oocyte-to-embryo transition

ELife
Masatoshi HaraT L Orr-Weaver

Abstract

The Drosophila Pan Gu (PNG) kinase complex regulates hundreds of maternal mRNAs that become translationally repressed or activated as the oocyte transitions to an embryo. In a previous paper (Hara et al., 2017), we demonstrated PNG activity is under tight developmental control and restricted to this transition. Here, examination of PNG specificity showed it to be a Thr-kinase yet lacking a clear phosphorylation site consensus sequence. An unbiased biochemical screen for PNG substrates identified the conserved translational repressor Trailer Hitch (TRAL). Phosphomimetic mutation of the PNG phospho-sites in TRAL reduced its ability to inhibit translation in vitro. In vivo, mutation of tral dominantly suppressed png mutants and restored Cyclin B protein levels. The repressor Pumilio (PUM) has the same relationship with PNG, and we also show that PUM is a PNG substrate. Furthermore, PNG can phosphorylate BICC and ME31B, repressors that bind TRAL in cytoplasmic RNPs. Therefore, PNG likely promotes translation at the oocyte-to-embryo transition by phosphorylating and inactivating translational repressors.

References

Aug 1, 1983·Developmental Biology·A P MahowaldJ H Caulton
Jul 27, 2001·Current Opinion in Chemical Biology·P J AlaimoK M Shokat
Dec 14, 2001·Proceedings of the National Academy of Sciences of the United States of America·X MorinW Chia
May 30, 2002·The Journal of Biological Chemistry·Colleen M NiswenderG Stanley McKnight
Oct 24, 2003·Nature·Jeffrey A UbersaxDavid O Morgan
Jun 3, 2004·Genome Research·Gavin E CrooksSteven E Brenner
Nov 1, 2006·The Journal of Biological Chemistry·Kimio J TanakaMasafumi Tsujimoto
Jan 3, 2007·Developmental Cell·Leah Vardy, Terry L Orr-Weaver
May 9, 2007·Nature Methods·Jasmina J AllenKevan M Shokat
Feb 1, 2008·Proceedings of the National Academy of Sciences of the United States of America·Justin D BlethrowKevan M Shokat
Mar 5, 2008·Biochimica Et Biophysica Acta·Helois E RadfordCornelia H de Moor
Aug 30, 2008·The International Journal of Biochemistry & Cell Biology·Aline MarnefMichael R Ladomery
Aug 25, 2009·Development·Wael Tadros, Howard D Lipshitz
Sep 14, 2010·Molecular Cell·Tracy NissanRoy Parker
Jun 29, 2011·Cold Spring Harbor Perspectives in Biology·Jessica R Von Stetina, Terry L Orr-Weaver
Nov 28, 2012·Nature Cell Biology·Timothy T WeilIlan Davis
Mar 19, 2013·Methods : a Companion to Methods in Enzymology·Timothy G CurranForest M White
Oct 8, 2013·Nature Methods·Joseph P O'SheaDaniel Schwartz
Nov 21, 2015·Methods in Molecular Biology·Daniel A RothenbergSebastian Lourido
Nov 3, 2016·Proceedings of the National Academy of Sciences of the United States of America·Young J YoonRobert H Singer

❮ Previous
Next ❯

Citations

May 24, 2018·Wiley Interdisciplinary Reviews. RNA·Debadrita Roy, Purusharth I Rajyaguru
Jun 24, 2020·Emerging Topics in Life Sciences·M Sankaranarayanan, Timothy T Weil
Apr 27, 2021·Frontiers in Molecular Biosciences·Jennifer A Schisa, Mohamed T Elaswad

❮ Previous
Next ❯

Methods Mentioned

BETA
peptide library
immunoprecipitation
confocal microscopy

Software Mentioned

Scaffold
WebLogo
Mascot
FlyTrap
CAMV
GENEWIZ
Proteome Discoverer
Quantity One

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.