Biology subjects

Pisliakov, A.

Publications and source records attributed to Pisliakov, A..

3 recordsLinked to original sources

bioRxiv2025

CaMKII-RNMT axis directs activity-dependent control of RNA dynamics in neurons

In neurons, mRNAs are transported into axons and dendrites for local translation at synapses. Diverse proteins support the transport of specific mRNAs, however, mechanisms co-ordinating mRNA translocation are unclear. We report that that CaMKII (Ca2+/calmodulin-dependent protein kinase II) is a key regulator of RNA dynamics through activity-dependent phosphorylation of the RNA cap guanine-7 methyltransferase, RNMT. Following RNA cap methylation in the nucleus, RNMT is retained on specific mRNAs. On stimulation, RNMT translocates into the cytoplasm, increasing levels of locally translated mRNAs. In the cytoplasm, CaMKII phosphorylates RNMT Thr317 on the active site, which inhibits methyltransferase activity and targets RNMT for degradation, thus limiting cytoplasmic RNMT function. RNMT mutants protected from CaMKII-dependent degradation increase locally translated, cytoplasmic mRNAs and accelerate neuronal morphogenesis. RNMT Thr317 phospho-mimic co-ordinately decreases locally translated mRNAs in the cytoplasm and reduces differentiation. The CaMKII-RNMT relationship links neuronal activity to the spatial regulation of gene expression in neurons. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC="FIGDIR/small/685591v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@b97c4borg.highwire.dtl.DTLVardef@18f38eaorg.highwire.dtl.DTLVardef@1e1bcb0org.highwire.dtl.DTLVardef@12ac7c7_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2020

Modelling the active SARS-CoV-2 helicase complex as a basis for structure-based inhibitor design

Having claimed over 1 million lives worldwide to date, the ongoing COVID-19 pandemic has created one of the biggest challenges to develop an effective drug to treat infected patients. Among all the proteins expressed by the virus, RNA helicase is a fundamental protein for viral replication, and it is highly conserved among the coronaviridae family. To date, there is no high-resolution structure of helicase bound with ATP and RNA. We present here structural insights and molecular dynamics (MD) simulation results of the SARS-CoV-2 RNA helicase both in its apo form and in complex with its natural substrates. Our structural information of the catalytically competent helicase complex provides valuable insights for the mechanism and function of this enzyme at the atomic level, a key to develop specific inhibitors for this potential COVID-19 drug target.

biochemistry↗

bioRxiv2019

A two-lane mechanism for selective biological ammonium transport

The transport of charged molecules across biological membranes faces the dual problem of accommodating charges in a highly hydrophobic environment while maintaining selective substrate translocation. A particular controversy has existed around the mechanism of ammonium exchange by the ubiquitous Amt/Mep/Rh transporter family, an essential process in all kingdoms of life. Here, using a combination of electrophysiology, yeast functional complementation and extended molecular dynamics simulations, we reveal a unique two-lane pathway for electrogenic NH4+ transport in two archetypal members of the family. The pathway underpins a mechanism by which charged H+ and neutral NH3 are carried separately across the membrane after NH4+ deprotonation. This mechanism defines a new principle of achieving transport selectivity against competing ions in a biological transport process.

biochemistry↗