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Elusive Trans-Acting Factors Which Operate with Type I (Poliovirus-like) IRES Elements
Dmitry E Andreev1,2, Michael Niepmann3, Ivan N Shatsky2
1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 117997 Moscow, Russia.
International Journal of Molecular Sciences
|December 23, 2022
Summary
Type I Internal Ribosome Entry Site (IRES) elements, crucial for cap-independent translation, are poorly understood. This study identifies Poly(rC) binding protein 2 (PCBP2), Glycyl-tRNA synthetase (GARS), and CSDE1 as key regulators of type I IRES activity.
Area of Science:
- Molecular Biology
- Virology
- Biochemistry
Background:
- Internal initiation of translation via Internal Ribosome Entry Site (IRES) elements was discovered in 1988.
- Type I IRES elements, like those in poliovirus mRNA's 5' untranslated region (5'UTR), direct translation initiation at internal start codons independently of the mRNA cap structure.
- Despite their early discovery, the host factors (IRES trans-acting factors, ITAFs) regulating type I IRES activity in vivo remain largely uncharacterized.
Purpose of the Study:
- To elucidate the specific host proteins that regulate the activity of type I IRES elements.
- To provide a comprehensive overview of recent and historical findings on type I IRES regulation.
Main Methods:
- Review and analysis of existing literature on type I IRES elements.
- Experimental investigation (implied) to identify and validate regulatory ITAFs.
Main Results:
- Poly(rC) binding protein 2 (PCBP2) is identified as a major regulator of type I IRES activity.
- Glycyl-tRNA synthetase (GARS) is identified as a major regulator of type I IRES activity.
- Cold Shock Domain Containing E1 (CSDE1), also known as UNR, is identified as a major regulator of type I IRES activity.
Conclusions:
- PCBP2, GARS, and CSDE1 are confirmed as key ITAFs essential for the full in vivo activity of type I IRES elements.
- This research clarifies the regulatory mechanisms of a fundamental biological process in viral and potentially cellular translation.
- Further research into these ITAFs can lead to a deeper understanding of translation control.
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