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Novel insights into biological roles of inducible cAMP early repressor ICER
ID Režen, Tadeja (Author), ID Prosenc Zmrzljak, Uršula (Author), ID Bensa, Tjaša (Author), ID Cvitanović Tomaš, Tanja (Author), ID Cirnski, Katarina (Author), ID Stojan, Jure (Author), ID Rozman, Damjana (Author)

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Abstract
ICER corresponds to a group of alternatively spliced Inducible cAMP Early Repressors with high similarity, but multiple roles, including in circadian rhythm, and are involved in attenuation of cAMPdependent gene expression. We present experimental and in silico data revealing biological differences between the isoforms with exon gamma (ICER) or without it (ICERγ). Both isoforms are expressed in the liver and the adrenal glands and can derive from differential splicing. In adrenals the expression is circadian, with maximum at ZT12 and higher amplitude of Icerγ. In the liver, the expression of Icerγ is lower than Icer in the 24 h time frame. Icer mRNA has a delayed early response to forskolin. The longer ICER protein binds to three DNA grooves of the Per1 promoter, while ICERγ only to two, as deduced by molecular modelling. This is in line with gel shift competition assays showing stronger binding of ICER to Per1 promotor. Only Icerγ siRNA provoked an increase of Per1 expression. In conclusion, we show that ICER and ICERγ have distinct biochemical properties in tissue expression, DNA binding, and response to forskolin. Data are in favour of ICERγ as the physiologically important form in hepatic cells where weaker binding of repressor might be preferred in guiding the cAMP-dependent response.

Language:English
Keywords:circadian rhythm, repressor ICER, biological roles, ICER, ICERγ, isoform, splicing, circadian expression
Work type:Article
Typology:1.01 - Original Scientific Article
Organization:MF - Faculty of Medicine
Publication status:Published
Publication version:Version of Record
Year:2020
Number of pages:Str. 396-401
Numbering:Vol. 530, iss. 2
PID:20.500.12556/RUL-137797 This link opens in a new window
UDC:61
ISSN on article:0006-291X
DOI:10.1016/j.bbrc.2020.05.017 This link opens in a new window
COBISS.SI-ID:21943811 This link opens in a new window
Publication date in RUL:01.07.2022
Views:705
Downloads:73
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Record is a part of a journal

Title:Biochemical and biophysical research communications
Shortened title:Biochem. biophys. res. commun.
Publisher:Elsevier
ISSN:0006-291X
COBISS.SI-ID:3265551 This link opens in a new window

Licences

License:CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Link:http://creativecommons.org/licenses/by-nc-nd/4.0/
Description:The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

Language:Slovenian
Keywords:cirkadijski ritem, represorja ICER, biološka vloga

Projects

Funder:ARRS - Slovenian Research Agency
Project number:P1-0390
Name:Funkcijska genomika in biotehnologija za zdravje

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