Extended poly(A) tails are a shared feature of herpesvirus mRNAs
Erik Fuhrmann1,2, Sae Toda1,3, Jonas Leins1
1Institute of Virology, Hannover Medical School, Hannover, Germany.
Abstract:
Poly(A) tails are present on most cellular and viral mRNAs, providing a platform for poly(A)-binding proteins that stimulate translation and regulate the deadenylation and stability of transcripts in the cytoplasm. Here we leverage nanopore direct RNA sequencing to analyse the distribution of poly(A) tail lengths on cellular and viral mRNAs across Herpesviridae and other DNA and RNA virus infections. We find that herpesvirus mRNA poly(A) tails are consistently longer than those on cellular and other viral transcripts, presenting a previously unrecognized yet widespread mechanism to potentially advantage herpesviral gene expression. This contrasts with the templated poly(A) tails on coronavirus RNAs and those on cytoplasmically transcribed poxviral mRNAs, which are more similar in length to those on host mRNAs. Herpesviral noncoding RNAs display differential poly(A) tailing patterns while individual herpesviral mRNAs also show variation in the extent to which their poly(A) tail lengths change during the virus lifecycle, suggestive of additional uncharacterised layers of poly(A) tail length regulation. Importantly, while we detect non-adenosine nucleotides within herpesviral poly(A) tails, which are known to oppose deadenylase activity, this "mixed tailing" is not at sufficient frequency to explain the widespread extended tails of herpesvirus mRNAs.
Insights
Herpesviruses possess unusually long poly(A) tails on their messenger RNAs (mRNAs), unlike other viruses and host cells. This extended polyadenylation may enhance herpesviral gene expression.
Area of Science:
- Molecular Biology
- Virology
- Genomics
Background:
- Poly(A) tails on messenger RNAs (mRNAs) are crucial for translation, stability, and deadenylation in the cytoplasm.
- Poly(A)-binding proteins interact with these tails to regulate gene expression.
Purpose of the Study:
- To investigate and compare poly(A) tail length distributions across various viral and cellular mRNAs.
- To explore the role of poly(A) tail length in herpesvirus gene expression.
Main Methods:
- Utilized nanopore direct RNA sequencing.
- Analyzed poly(A) tail length distributions on cellular and viral mRNAs during infections with Herpesviridae, other DNA viruses, and RNA viruses.
Main Results:
- Herpesvirus mRNAs exhibit significantly longer poly(A) tails compared to cellular and other viral mRNAs.
- Coronavirus and poxviral mRNAs show poly(A) tail lengths similar to host mRNAs.
- Herpesviral noncoding RNAs display varied poly(A) tailing patterns.
- Mixed non-adenosine nucleotides in herpesviral poly(A) tails were insufficient to explain extended tail lengths.
Conclusions:
- Herpesviruses employ a widespread mechanism of extended poly(A) tails on their mRNAs, potentially conferring a gene expression advantage.
- This contrasts with other viral polyadenylation strategies and suggests uncharacterized regulatory layers.
- The extended poly(A) tails are a distinct feature of herpesviral gene expression, not fully explained by mixed nucleotide composition.
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