HNRNPM promotes protein synthesis via an interaction with stem-loop 5 in the SARS-CoV-2 5'-UTR

Golagha, J.; Wieja, M.; Biedenkopf, N.; Weigand, J. E.

doi:10.64898/2026.10.05.756635

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bioRxiv · 10.64898/2026.10.05.756635

HNRNPM promotes protein synthesis via an interaction with stem-loop 5 in the SARS-CoV-2 5'-UTR

Golagha, J.·Wieja, M.·Biedenkopf, N.·Weigand, J. E.

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Abstract

The 5'-untranslated region (5'-UTR) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly structured and comprises five conserved stem-loops that serve as cis-acting regulatory elements. During infection, host proteins are recruited to these elements and regulate multiple steps during the viral life cycle. Stem-loop 5 (SL5) is highly conserved among different alpha- and betacoronaviruses and includes the start codon of non-structural protein 1 (nsp1). However, the function of SL5 in viral replication and its interacting proteins remain to be determined. Here, we identified heterogeneous nuclear ribonucleoprotein M (HNRNPM) as a host protein functionally interacting with SL5. HNRNPM translocates into the cytoplasm during SARS-CoV-2 infection and promotes protein synthesis from the viral 5'-UTR. Mutations in the lower stem of SL5 impair HNRNPM binding and reduce protein synthesis. Notably, the interaction between HNRNPM and SL5 is conserved among different alpha- and betacoronaviruses. Our findings indicate that HNRNPM is an important host factor that regulates viral translation to promote SARS-CoV-2 replication.

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Golagha, J., Wieja, M., Biedenkopf, N., Weigand, J. E.. 2026-10-05. HNRNPM promotes protein synthesis via an interaction with stem-loop 5 in the SARS-CoV-2 5'-UTR. https://doi.org/10.64898/2026.10.05.756635

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