PMID- 27790092
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1662-5099 (Print)
IS  - 1662-5099 (Electronic)
IS  - 1662-5099 (Linking)
VI  - 9
DP  - 2016
TI  - Upstream Open Reading Frames Located in the Leader of Protein Kinase Mzeta mRNA 
      Regulate Its Translation.
PG  - 103
LID - 103
AB  - For protein synthesis that occurs locally in dendrites, the translational control 
      mechanisms are much more important for neuronal functioning than the 
      transcription levels. Here, we show that uORFs (upstream open reading frames) in 
      the 5' untranslated region (5'UTR) play a critical role in regulation of the 
      translation of protein kinase Mzeta (PKMzeta). Elimination of these uORFs activates 
      translation of the reporter protein in vitro and in primary cultures of rat 
      hippocampal neurons. Using cell-free translation systems, we demonstrate that 
      translational initiation complexes are formed only on uORFs. Further, we address 
      the mechanism of translational repression of PKMzeta translation, by uORFs. We 
      observed an increase in translation of the reporter protein under the control of 
      PKMzeta leader in neuronal culture during non-specific activation by picrotoxin. We 
      also show that such a mechanism is similar to the mechanism seen in cell stress, 
      as application of sodium arsenite to neuron cultures induced translation of mRNA 
      carrying PKMzeta 5'UTR similarly to picrotoxin activation. Therefore, we suppose 
      that phosphorylation of eIF2a, like in cell stress, is a main regulator of PKMzeta 
      translation. Altogether, our findings considerably extend our understanding of 
      the role of uORF in regulation of PKMzeta translation in activated neurons, 
      important at early stages of LTP.
FAU - Bal, Natalia V
AU  - Bal NV
AD  - Cellular Neurobiology of Learning Laboratory, Institute of Higher Nervous 
      Activity and Neurophysiology, Russian Academy of Sciences Moscow, Russia.
FAU - Susorov, Denis
AU  - Susorov D
AD  - Laboratory of Mechanisms and Control of Translation, Engelhardt Institute of 
      Molecular Biology, Russian Academy of SciencesMoscow, Russia; Faculty of 
      Bioengineering and Bioinformatics, M. V. Lomonosov Moscow State UniversityMoscow, 
      Russia.
FAU - Chesnokova, Ekaterina
AU  - Chesnokova E
AD  - Cellular Neurobiology of Learning Laboratory, Institute of Higher Nervous 
      Activity and Neurophysiology, Russian Academy of Sciences Moscow, Russia.
FAU - Kasianov, Artem
AU  - Kasianov A
AD  - Laboratory of System Biology and Computational Genetics, Vavilov Institute of 
      General Genetics, Russian Academy of Sciences Moscow, Russia.
FAU - Mikhailova, Tatiana
AU  - Mikhailova T
AD  - Laboratory of Mechanisms and Control of Translation, Engelhardt Institute of 
      Molecular Biology, Russian Academy of Sciences Moscow, Russia.
FAU - Alkalaeva, Elena
AU  - Alkalaeva E
AD  - Laboratory of Mechanisms and Control of Translation, Engelhardt Institute of 
      Molecular Biology, Russian Academy of Sciences Moscow, Russia.
FAU - Balaban, Pavel M
AU  - Balaban PM
AD  - Cellular Neurobiology of Learning Laboratory, Institute of Higher Nervous 
      Activity and Neurophysiology, Russian Academy of Sciences Moscow, Russia.
FAU - Kolosov, Peter
AU  - Kolosov P
AD  - Cellular Neurobiology of Learning Laboratory, Institute of Higher Nervous 
      Activity and Neurophysiology, Russian Academy of Sciences Moscow, Russia.
LA  - eng
PT  - Journal Article
DEP - 20161013
PL  - Switzerland
TA  - Front Mol Neurosci
JT  - Frontiers in molecular neuroscience
JID - 101477914
PMC - PMC5061749
OTO - NOTNLM
OT  - PKMzeta
OT  - eIF2a phosphorylation
OT  - local protein synthesis
OT  - translational control
OT  - uORF
EDAT- 2016/10/30 06:00
MHDA- 2016/10/30 06:01
PMCR- 2016/01/01
CRDT- 2016/10/30 06:00
PHST- 2016/07/14 00:00 [received]
PHST- 2016/09/30 00:00 [accepted]
PHST- 2016/10/30 06:00 [pubmed]
PHST- 2016/10/30 06:01 [medline]
PHST- 2016/10/30 06:00 [entrez]
PHST- 2016/01/01 00:00 [pmc-release]
AID - 10.3389/fnmol.2016.00103 [doi]
PST - epublish
SO  - Front Mol Neurosci. 2016 Oct 13;9:103. doi: 10.3389/fnmol.2016.00103. eCollection 
      2016.