Elsevier

Current Opinion in Virology

Volume 1, Issue 5, November 2011, Pages 373-380
Current Opinion in Virology

3′ Cap-independent translation enhancers of positive-strand RNA plant viruses

https://doi.org/10.1016/j.coviro.2011.10.002Get rights and content

Positive-strand RNA plant viruses that are neither 5′-capped nor 3′-polyadenylated use nontraditional mechanisms to recruit ribosomes to the 5′-end of their viral genomes. One strategy employed by some of these viruses involves a type of RNA element, termed the 3′ cap-independent translation enhancer (3′CITE), located in or near the 3′-untranslated region of viral RNA genomes. 3′CITEs function to mediate efficient translation of 5′-proximally encoded viral proteins and function by recruiting either translation initiation factors or the 60S ribosomal subunit to the viral RNA. Recent mechanistic and structural studies have revealed important new insights and details of how 3′CITEs are able to facilitate viral translation and allow these viruses to compete efficiently against cellular mRNAs for the host translational machinery.

Highlights

Plant viruses utilize unique mechanisms to hijack the host translational machinery. ► 3′CITEs are a class of RNA element that performs this function in Tombusviridae. ► 3′CITEs operate by binding to translation initiation factors or ribosomal subunits. ► Major advances in the field as well as future prospects are discussed herein.

Introduction

To be translated efficiently, most eukaryotic mRNAs contain a 5′-m7GpppN cap structure and a 3′-poly(A) tail. The cap is bound by eukaryotic translation initiation factor 4E (eIF4E) via contacts that include stacking interactions between the 7-methyl guanine of the cap and two tryptophan residues in the eIF4E cap-binding pocket [1, 2]. eIF4E also interacts with eIF4G, forming the eIF4F complex [3]. In plants, the purified eIF4F complex does not include eIF4A [4], whereas this helicase does copurify with the complex isolated from mammals [5]. In both plants and animals, eIF4A is thought to aid in unwinding of the mRNA leader sequence during ribosome scanning. eIF4G acts as a scaffolding protein by binding other initiation factors including eIF3, which recruits the 43S subunit of the ribosome [4], as well as the poly(A)-binding protein (PABP), which binds simultaneously to the poly(A) tail [6]. The 5′cap-eIF4F-PABP-poly(A) tail interaction circularizes the mRNA and enhances translation by stabilizing the interaction between eIF4F and the cap [7].

The RNA genomes of many positive-strand (messenger-sensed) RNA plant viruses are neither 5′-capped nor 3′-polyadenylated and, thus, must employ alternative translation mechanisms to effectively compete for host ribosomes [8]. For some RNA viruses, including members of the Tombusviridae and Luteoviridae families (Table 1), this involves RNA elements in their viral genomes within or near the 3′-untranslated region (3′UTR). These RNA structures, termed 3′ cap-independent translational enhancers (3′CITEs), are essential for efficient translation of these RNA genomes [9]. Different 3′CITEs possess distinctive properties; however, they appear to share some general mechanistic principles that include: first, recruitment of components of the translation machinery via 3′CITE binding, second, communication of the 3′CITE with the viral 5′UTR and third, positioning of the ribosomal subunits at the 5′-end of the viral genome. Collectively, these 3′CITE-mediated events facilitate efficient initiation of translation and, as described herein, recent studies have begun to shed light on the mechanisms by which these RNA elements operate.

Section snippets

Structural classes of 3′CITE

The 3′CITEs identified in uncapped, nonpolyadenylated RNA viruses to date have been grouped into six major classes based on sequence and secondary structure (reviewed in [9]) (Table 1). The first 3′CITE was discovered in satellite Tobacco necrosis virus (sTNV) and was called the translation enhancer domain (TED) [10]. The sTNV TED consists of a 93 nt long sequence that is predicted to form an extended stem-loop (SL) structure (Table 1). In contrast, the 3′CITE in the luteovirus Barley yellow

3′CITE recruitment of translational machinery

Shortly after their discovery, it was proposed that 3′CITEs might function by recruiting translation-related factors to the viral RNA [30, 31]. Of the interactions reported so far, most 3′CITEs bind to the initiation factor complex eIF4F [19••, 27•, 32, 33] (Table 1), consistent with their function as a 5′-cap replacement. In fact, the PTE of PEMV may represent a true 5′-cap mimic, as it binds eIF4E with high affinity (Kd  58 nm) [16] and is proposed to do so via the highly flexible guanine

Mechanisms of translational enhancement

Translation is initiated at the 5′-end of viral genomes, thus the distal location of the 3′CITEs that recruit the translational machinery seems counterintuitive. Indeed, this configuration suggests that there must be some form of 5′–3′ communication to facilitate efficient translation at the 5′-end. For most 3′CITEs, this appears to be achieved through formation of an intramolecular RNA–RNA interaction, where sequence in the 3′CITE base pairs with complementary sequence in the 5′UTR of the

Perspectives and future directions

Recent studies have begun to reveal detailed mechanistic insights into how plant RNA virus 3′CITEs enhance translation initiation of 5′-proximal viral genes over long distances. Despite the progress made to date, many questions related to 3′CITE structure, function and evolution remain. Structurally, high-resolution models exist for only two classes of 3′CITE, the PTE and TSS [19••, 21••], thus additional effort is required to solve the higher-order structures of the remaining known classes of

Plant versus animal cap-independent translation

Like their plant virus counterparts, animal plus-strand RNA viruses that lack a 5′cap also employ unconventional strategies to recruit host ribosomes. Currently, no 3′CITEs have been identified in uncapped animal viruses. Instead, these viruses typically contain internal ribosome entry sites (IRESes) in their 5′UTRs [43]. Animal virus IRESes, which are described in the companion article by Reineke and Lloyd [44], provide an interesting contrast to 3′CITEs. An obvious difference between the two

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

We thank Allen Miller and members of our laboratory for reviewing the manuscript and providing useful comments. BLN is supported by an NSERC Canada Graduate Scholarship and the research in our laboratory is supported by grants from NSERC, CFI and CRC to KAW. We apologize to those researchers whose works were not presented due to page restrictions.

References (45)

  • B.L. Nicholson et al.

    Tombusvirus recruitment of host translational machinery via the 3′ UTR

    RNA

    (2010)
  • V. Truniger et al.

    Mechanism of plant eIF4E-mediated resistance against a Carmovirus (Tombusviridae): cap-independent translation of a viral RNA controlled in cis by an (a)virulence determinant

    Plant J

    (2008)
  • S. Wang et al.

    A viral sequence in the 3′-untranslated region mimics a 5′ cap in facilitating translation of uncapped mRNA

    EMBO J

    (1997)
  • S. Sarawaneeyaruk et al.

    Host-dependent roles of the viral 5′ untranslated region (UTR) in RNA stabilization and cap-independent translational enhancement mediated by the 3′UTR of Red clover necrotic mosaic virus RNA1

    Virology

    (2009)
  • J.K. Barry et al.

    A-1 ribosomal frameshift element that requires base pairing across four kilobases suggests a mechanism of regulating ribosome and replicase traffic on a viral RNA

    Proc Natl Acad Sci U S A

    (2002)
  • Z. Yao et al.

    A computational pipeline for high-throughput discovery of cis-regulatory noncoding RNA in prokaryotes

    PLoS Comput Biol

    (2007)
  • H. Matsuo et al.

    Structure of translation factor eIF4E bound to m7GDP and interaction with 4E-binding protein

    Nat Struct Biol

    (1997)
  • A.C. Gingras et al.

    eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation

    Annu Rev Biochem

    (1999)
  • K.S. Browning

    The plant translational apparatus

    Plant Mol Biol

    (1996)
  • H. Imataka et al.

    A newly identified N-terminal amino acid sequence of human eIF4G binds poly(A)-binding protein and functions in poly(A)-dependent translation

    EMBO J

    (1998)
  • W.A. Miller et al.

    The amazing diversity of cap-independent translation elements in the 3′-untranslated regions of plant viral RNAs

    Biochem Soc Trans

    (2007)
  • X. Danthinne et al.

    The 3′ untranslated region of satellite tobacco necrosis virus RNA stimulates translation in vitro

    Mol Cell Biol

    (1993)
  • Cited by (0)

    View full text