Cap-related modifications of RNA regulate binding to IFIT proteins.

Geng, Jingping; Chrabaszczewska, Magdalena; Kurpiejewski, Karol; Stankiewicz-Drogon, Anna; Jankowska-Anyszka, Marzena; Darzynkiewicz, Edward; Grzela, Renata

Geng, Jingping; Chrabaszczewska, Magdalena; Kurpiejewski, Karol; Stankiewicz-Drogon, Anna; Jankowska-Anyszka, Marzena; Darzynkiewicz, Edward; Grzela, Renata.

Afiliación

Geng J; Interdisciplinary Laboratory of Molecular Biology and Biophysics, Centre of New Technologies, University of Warsaw, 02-097 Warsaw, Poland.
Chrabaszczewska M; Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, 02-093 Warsaw, Poland.
Kurpiejewski K; Faculty of Chemistry, University of Warsaw, 02-093 Warsaw, Poland.
Stankiewicz-Drogon A; Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, 02-093 Warsaw, Poland.
Jankowska-Anyszka M; Faculty of Chemistry, University of Warsaw, 02-093 Warsaw, Poland.
Darzynkiewicz E; Interdisciplinary Laboratory of Molecular Biology and Biophysics, Centre of New Technologies, University of Warsaw, 02-097 Warsaw, Poland.
Grzela R; Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, 02-093 Warsaw, Poland.

RNA ; 30(10): 1292-1305, 2024 Sep 16.

Article en En | MEDLINE | ID: mdl-39009378

ABSTRACT

ABSTRACT

All cells in our body are equipped with receptors to recognize pathogens and trigger a rapid defense response. As a result, foreign molecules are blocked, and cells are alerted to the danger. Among the many molecules produced in response to viral infection are interferon-induced proteins with tetratricopeptide repeats (IFITs). Their role is to recognize foreign mRNA and eliminate it from the translational pool of transcripts. In the present study, we used biophysical methods to characterize the interactions between the IFIT1 protein and its partners IFIT2 and IFIT3. IFIT1 interacts with IFIT3 with nanomolar binding affinity, which did not change significantly in the presence of the preformed IFIT2/3 complex. The interactions between IFIT2 and IFIT3 and IFIT1 and IFIT2 were one order of magnitude weaker. We also present kinetic data of the interactions between the IFIT protein complex and short RNA bearing various modifications at the 5' end. We show kinetic parameters for interaction between the IFIT complex and RNA with m6Am modification. The results show that the cap-adjacent m6Am modification is a stronger signature than cap1 alone. It blocks the formation of a complex between IFIT proteins and m7Gpppm6Am-RNA much more effectively than other cap modifications. In contrast, m6A in the 5'UTR is not recognized by IFIT proteins and does not contribute to translation repression by IFIT proteins. The data obtained are important for understanding the regulation of expression of genetic information. They indicate that 2'-O and m6Am modifications modulate the availability of mRNA molecules for proteins of innate immune response.

Asunto(s)

Proteínas Adaptadoras Transductoras de Señales; Unión Proteica; Proteínas de Unión al ARN; Proteínas de Unión al ARN/metabolismo; Proteínas de Unión al ARN/genética; Humanos; Proteínas Adaptadoras Transductoras de Señales/metabolismo; Proteínas Adaptadoras Transductoras de Señales/genética; Caperuzas de ARN/metabolismo; Caperuzas de ARN/genética; ARN Mensajero/genética; ARN Mensajero/metabolismo; Proteínas Portadoras/metabolismo; Proteínas Portadoras/genética; Proteínas Reguladoras de la Apoptosis/metabolismo; Proteínas Reguladoras de la Apoptosis/genética; Cinética; Proteínas/metabolismo; Proteínas/genética; Péptidos y Proteínas de Señalización Intracelular/metabolismo; Péptidos y Proteínas de Señalización Intracelular/genética

Palabras clave

CAP1; IFIT proteins; M6AM; cap modification; innate immune response

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Unión Proteica / Proteínas de Unión al ARN / Proteínas Adaptadoras Transductoras de Señales Límite: Humans Idioma: En Revista: RNA Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: Polonia Pais de publicación: Estados Unidos

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