# Determining the impact of respiratory syncytial virus M2-1 protein on post-transcriptional regulation of cellular and viral mRNAs > **NIH NIH R21** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2024 · $206,250 ## Abstract SUMMARY Respiratory syncytial virus (RSV) is a major cause of respiratory disease. Its impact is greatest in the young, the elderly and the immunocompromised. As yet, there are no vaccines to prevent infection, or effective antivirals to treat those who become infected. A greater understanding of the viral factors that facilitate replication and impact pathogenesis could aid development of effective interventions. RSV is a member of the non-segmented negative strand RNA viruses. Its polymerase complex transcribes the viral genome to produce subgenomic, capped and polyadenylated mRNAs. A key factor in the RSV transcription machinery is the viral M2-1 protein, an elongation factor, which is required for the polymerase to complete transcription of longer genes and in doing so to access downstream regions of the genome. While this transcription elongation function of M2-1 and its structural and biochemical properties are well established, recent findings have hinted at an additional, unexplored role for M2-1 in post transcriptional regulation. RSV transcribes its genome in cytoplasmic inclusions. High resolution microscopy studies revealed that M2-1 accumulates together with newly synthesized RSV mRNAs and cellular translation proteins, eIF4G and cytoplasmic poly A binding protein, within inclusion body associated granules that are spatially separated from the RSV genome RNAs and polymerase. This finding suggests that following transcription of an RSV mRNA, M2-1 might remain associated with it to facilitate transfer to the translation machinery. Further, recent work revealed that in addition to binding to RSV mRNAs, M2-1 binds to specific regions within a subset of cellular mRNAs, including mRNAs involved in immune responses to viral infection. Intriguingly, a key feature of M2-1 is a Zn-finger domain containing an unusual cysteine-cysteine-cysteine-histidine (CCCH) motif, that is typically found in cellular proteins involved in post-transcriptional regulation of mRNA involved in immune responses. These findings, combined with published data that shows that RSV M2-1 interacts with cellular proteins involved in mRNA metabolism, leads us to the hypothesis that M2-1 exerts a post-transcriptional role in RSV and/or cellular gene expression. The goal of this project is to test this hypothesis. Aim 1 will determine if M2-1 affects RSV protein expression independently of its effects on RSV transcription elongation. Aim 2 will characterize the effects of RSV M2-1 on protein expression from CXCL5 and CANX, two of its cellular mRNA targets. Together, these experiments will yield new insight into the role of the RSV M2-1 protein with implications for understanding a key aspect of the RSV replication cycle and mechanisms underlying RSV pathogenesis. In addition, given that the distinctive Zn-finger CCCH motif is shared in proteins of other related viruses, this project could have an impact beyond RSV biology, providing novel insight into the filoviruses and othe... ## Key facts - **NIH application ID:** 10906739 - **Project number:** 5R21AI174597-02 - **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS - **Principal Investigator:** Rachel Fearns - **Activity code:** R21 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $206,250 - **Award type:** 5 - **Project period:** 2023-08-14 → 2026-07-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10906739 ## Citation > US National Institutes of Health, RePORTER application 10906739, Determining the impact of respiratory syncytial virus M2-1 protein on post-transcriptional regulation of cellular and viral mRNAs (5R21AI174597-02). Retrieved via AI Analytics 2026-08-11 from https://api.ai-analytics.org/grant/nih/10906739. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*