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Cap-related modifications of RNA regulate binding to IFIT proteins.
Jingping Geng1, Magdalena Chrabaszczewska2, Karol Kurpiejewski3
1Interdisciplinary Laboratory of Molecular Biology and Biophysics, Centre of New Technologies, University of Warsaw, 02-097 Warsaw, Poland.
RNA (New York, N.Y.)
|July 15, 2024
Summary
Interferon-induced proteins with tetratricopeptide repeats (IFITs) recognize viral mRNA. Cap-adjacent m6Am modification strongly blocks IFIT protein binding, impacting innate immune response regulation.
Area of Science:
- Immunology
- Molecular Biology
- Virology
Background:
- Cells possess receptors to detect pathogens and initiate defense responses.
- Interferon-induced proteins with tetratricopeptide repeats (IFITs) are crucial in antiviral defense by targeting foreign mRNA.
Purpose of the Study:
- To characterize the biophysical interactions of IFIT1 with IFIT2 and IFIT3.
- To investigate the role of RNA modifications, particularly m6Am, in IFIT protein recognition and mRNA binding.
Main Methods:
- Biophysical methods were employed to study protein-protein interactions.
- Kinetic analyses were performed to assess IFIT complex interactions with modified RNA.
Main Results:
- IFIT1 exhibits nanomolar binding affinity with IFIT3.
- The cap-adjacent m6Am modification on RNA significantly blocks IFIT protein complex formation more effectively than other cap modifications.
- m6A in the 5'UTR does not influence IFIT recognition or translation repression.
Conclusions:
- m6Am modification acts as a strong signal recognized by IFIT proteins, influencing mRNA availability.
- These findings enhance understanding of genetic information expression regulation and innate immunity.
- 2'-O and m6Am modifications modulate mRNA accessibility for innate immune response proteins.
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