CORDIS - EU research results
CORDIS

Non-canonical RNA caps - cellular reaction to environment and stress

Project description

New class of RNA caps and their role in cellular response to infection and stress

The EU-funded StressRNaction project is investigating the role of newly discovered non-canonical RNA caps, dinucleoside polyphosphates (NpnNs), in prokaryotes and eukaryotes. These 5' termini specially altered nucleotides, or caps, are vital for the creation of mature messenger RNA and for translation during protein synthesis. The methylated NpnN caps discovered by project researchers stabilise RNA in Escherichia coli in the stationary phase and can be found in mammalian cells. The objective is to develop selective capturing techniques to identify NpnN–RNA sequences and the interacting partners. The project aims to understand the metabolism of NpnN caps, their role in the immune response to viruses and bacteria, and stress conditions in prokaryotic and eukaryotic cells.

Objective

The goal of this project is to understand the role of non-canonical RNA caps (mainly dinucleoside polyphosphates = NpnNs) in prokaryotes and eukaryotes. The 5' termini of the RNA are critical structures and are the least characterized among RNA modifications. In this project, we will develop selective capturing techniques for identification of NpnN-RNA sequences and identify the interacting partners of NpnN-RNA. Furthermore, we will reveal their metabolism and their role in cellular reaction to stress conditions in prokaryotes and eukaryotes.
Until recently only canonical structures, NAD or CoA have been known as 5' RNA caps. We discovered an entirely new class of 5' RNA caps - dinucleoside polyphosphates (NpnN) in prokaryotic and eukaryotic cells. Based on our preliminary data we know that methylated NpnN caps stabilize RNA of E. coli in the stationary phase and that some NpnN caps can also be found in mammalian cells. We do not yet know [1] the sequence of RNAs capped with NpnNs, [2] how many types of NpnN RNA caps exist in eukaryotes, [3] whether RNA stabilization is their only role, [4] why there are so many types of NpnN RNA caps (we identified nine in E. coli), [5] whether NpnN-RNA can be translated, etc.
The role of free NpnNs, identified fifty years ago, is yet to be elucidated. NpnNs are called alarmones, as their concentration increases under stress conditions. The mechanism by which the alarm is recognized in cells is unknown. I presume that their cellular effects are mediated by the RNA, where they serve as RNA caps. As such, they become an important part of RNA metabolism and can be recognized by various RNA interacting proteins, triggering additional effects in cellular metabolism. The presented project has the potential to solve the puzzle of the role of NpnNs and clarify the connection between RNA metabolism and immune response or virulence factors of viruses and bacteria.

Host institution

USTAV ORGANICKE CHEMIE A BIOCHEMIE, AV CR, V.V.I.
Net EU contribution
€ 1 497 425,00
Address
FLEMINGOVO NAM. 542/2
16610 Praha 6
Czechia

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Region
Česko Praha Hlavní město Praha
Activity type
Research Organisations
Links
Total cost
€ 1 497 425,00

Beneficiaries (1)