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 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 which do not correlate with nuclear localisation 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 utilize unusually long poly(A) tails on their messenger RNAs (mRNAs) to enhance gene expression. This extended polyadenylation, unlike in other viruses, provides a significant advantage during infection.
Area of Science:
- Molecular Biology
- Virology
- Genomics
Background:
- Poly(A) tails are crucial for mRNA stability, translation, and regulation.
- Most cellular and viral mRNAs possess poly(A) tails, but their lengths vary.
- Herpesviruses are known for complex gene expression strategies.
Purpose of the Study:
- To investigate poly(A) tail length distribution on viral and cellular mRNAs during various viral infections.
- To compare poly(A) tail lengths across different virus families, including Herpesviridae.
- To understand the role of poly(A) tail length in herpesviral gene expression advantage.
Main Methods:
- Nanopore direct RNA sequencing was employed to analyze poly(A) tail lengths.
- Comparative analysis of poly(A) tail distributions on cellular and viral mRNAs.
- Investigation across Herpesviridae, coronavirus, and poxvirus infections.
Main Results:
- Herpesvirus mRNAs exhibit significantly longer poly(A) tails compared to cellular and other viral mRNAs.
- Poly(A) tail lengths of coronaviruses and poxviruses are more similar to host mRNAs.
- Herpesviral noncoding RNAs show varied poly(A) tailing patterns, and individual mRNAs display dynamic tail length changes.
- Mixed nucleotide content in herpesviral poly(A) tails was insufficient to explain the extended lengths.
Conclusions:
- Extended poly(A) tails on herpesvirus mRNAs represent a widespread mechanism enhancing viral gene expression.
- This finding highlights a novel strategy employed by herpesviruses to gain a competitive advantage.
- Further research is needed to elucidate the uncharacterized regulatory mechanisms governing herpesviral poly(A) tail lengths.
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