The Functional Role of the 3' Untranslated Region and Poly(A) Tail of Duck Hepatitis A Virus Type 1 in Viral Replication and Regulation of IRES-Mediated Translation.

Jun-Hao Chen,Fu-Chang Li,Jing-Jing Lan,Rui-Hua Zhang,Sha-Sha Song,Zhi-Jing Xie,Shao-Li Lin,Peng-Fei Li,Ji-Ming Gao,Shi-Jin Jiang,Yu Wang

doi:10.3389/fmicb.2018.02250

Jun-Hao Chen, Fu-Chang Li + Show 9 more

Open Access

https://doi.org/10.3389/fmicb.2018.02250

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Abstract

The duck hepatitis A virus type 1 (DHAV-1) is a member of Picornaviridae family, the genome of the virus contains a 5′ untranslated region (5′ UTR), a large open reading frame that encodes a polyprotein precursor and a 3′ UTR followed by a poly(A) tail. The translation initiation of virus proteins depends on the internal ribosome-entry site (IRES) element within the 5′ UTR. So far, little information is known about the role of the 3′ UTR and poly(A) tail during the virus proliferation. In this study, the function of the 3′ UTR and poly(A) tail of DHAV-1 in viral replication and IRES-mediated translation was investigated. The results showed that both 3′ UTR and poly(A) tail are important for maintaining viral genome RNA stability and viral genome replication. During DHAV-1 proliferation, at least 20 adenines were required for the optimal genome replication and the virus replication could be severely impaired when the poly (A) tail was curtailed to 10 adenines. In addition to facilitating viral genome replication, the presence of 3′ UTR and poly(A) tail significantly enhance IRES-mediated translation efficiency. Furthermore, 3′ UTR or poly(A) tail could function as an individual element to enhance the DHAV-1 IRES-mediated translation, during which process, the 3′ UTR exerts a greater initiation efficiency than the poly(A)25 tail.

Highlights

The internal ribosome entry site (IRES) element possesses the function to direct cap-independent internal initiation of protein synthesis; the underlying mechanism might differ from that of the canonical cap-dependent translation initiation of the majority of cellular mRNAs (Belsham, 2009)
Based on the RNA stability result that poly(A)10 tail, and poly(A)15 tail and poly(A)20 viral RNA shared similar stability, it was confirmed that the change of viral genome copy number is due to the direct regulation of viral RNA replication by poly (A) tail
It has been demonstrated that the 3 UTR or poly(A) tail of picornaviruses is important for maintaining the viral genome replication and translation efficiency (Rohll et al, 1995; Todd et al, 1997; Dobrikova et al, 2006)

Summary

Introduction

The internal ribosome entry site (IRES) element possesses the function to direct cap-independent internal initiation of protein synthesis; the underlying mechanism might differ from that of the canonical cap-dependent translation initiation of the majority of cellular mRNAs (Belsham, 2009). Most eukaryotic mRNAs and many viral RNAs are capped and poly(A) tailed at both termini, thereby regulating translation efficiency individually, or in concert (Hentze, 1997; Sachs et al, 1997). The 3 End Affects DHAV-1 Propagation complex eukaryotic translation initiation factor 4F (eIF4F) for cellular mRNA translation initiation (Gingras et al, 1999). Picornavirus RNA is not 5 capped and the initiation of viral protein synthesis was termed internal initiation, which relies upon the IRES element within the 5 UTR (Belsham and Jackson, 2000). The DHAV1 IRES element is categorized as a type IV IRES, which is found essential for internal translation initiation (Pan et al, 2012)

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