Caps in Eukaryotic mRNAs: Mechanism of Formation of Reovirus mRNA 5′-Terminal m7GpppGm-C

https://doi.org/10.1016/S0079-6603(08)60905-8Get rights and content

Publisher Summary

This chapter discusses that blocked and methylated 5'-termini of reovirus mRNA are formed by viral cores at an early stage of transcription. Cores incubated in a complete transcription reaction mixture for 30 seconds synthesize the “cap” structure, m7GpppGm-C. The dinucleotide ppG-C functions as substrate for a core-associated guanylyltransferase and is converted to GpppG-C by addition of pG from pppG( GTP). For optimal conversion both the diphosphate terminus and phosphodiester bond are required. pG-C is not a substrate, but pppG-C is utilized after removal of the γ-phosphate by a core nucleotide phosphohydrolase. Methyltransferases, also present in cores, transfer methyl groups sequentially from S-adenosylmethionine to the 7-position of the 5'-terminal G of GpppG-C and to the 2'-OH of the penultimate G. The chapter reviews that GpppG-C is hydrolyzed by cores in the presence of pyrophosphate to ppG-C, the predominant 5'-terminal structure of reovirus mRNA made in the absence of S-adenosylmethionine. 7-Methylation prevents pyrophosphorolysis of m7GpppG-C, which may explain the increased proportion of blocked, methylated 5' termini in viral mRNA synthesized in the presence of S-adenosylmethionine. On the basis of these findings, it proposes a series of reactions for the synthesis of reovirus mRNA caps, and some characteristic features of the enzymes involved in these reactions are also discussed.

References (28)

  • G.W. Both et al.

    Cell

    (1975)
  • R.P. Perry et al.

    Cell

    (1975)
  • M. Salditt-Georgieff et al.

    Cell

    (1976)
  • S. Cory et al.

    JMB

    (1975)
  • T.S. Ro-Choi et al.

    JBC

    (1975)
  • Y. Furuichi et al.

    JBC

    (1976)
  • S.A. Martin et al.

    JBC

    (1975)
  • S.A. Martin et al.

    JBC

    (1975)
  • A.J. Shatkin et al.

    Cell

    (1976)
  • S. Muthukrishnan et al.

    Virology

    (1975)
  • A.J. Shatkin

    Cell

    (1976)
  • G.W. Both et al.

    PNAS

    (1975)
  • S. Muthukrishnan et al.

    Nature

    (1975)
  • E.D. Hickey et al.

    PNAS

    (1976)
  • Cited by (19)

    • Silencing and complementation of reovirus core protein μ2: Functional correlations with μ2-microtubule association and differences between virus- and plasmid-derived μ2

      2007, Virology
      Citation Excerpt :

      Combining these results, our working hypothesis is that, within infected cells, the μ2 protein is normally assembled into progeny particles, where its NTPase function is required for genome replication and/or secondary transcription, as well as for primary transcription once progeny virions are released and move on to infect new cells. In the case of transcription, the RTPase activity of μ2 may be instead or additionally required in 5′-capping of the plus-strand RNAs, i.e., for generating a diphosphorylated 5′ end on each RNA to which GMP is then linked by the guanylyltransferase λ2 (Cleveland et al., 1986; Furuichi et al., 1976; Mao and Joklik, 1991). Having successfully applied the siRNA approach, we are now in stronger position to perform a combination of future studies in vitro and in vivo to dissect the different roles of μ2 during infection.

    • Nucleoside and RNA Triphosphatase Activities of Orthoreovirus Transcriptase Cofactor μ2

      2004, Journal of Biological Chemistry
      Citation Excerpt :

      RTPase Activity of wt μ2—The capacity of wt μ2 to release the γ-phosphate from an NTP led us to hypothesize that μ2 may also release the 5′ γ-phosphate from an RNA molecule. mORV cores mediate such an RTPase activity, which yields a diphosphorylated RNA 5′ end (11, 49) for linkage to GMP by the λ2-associated guanylyltransferase (4, 11, 14, 15, 17, 18), as part of the mRNA capping process. The RTPase activity has been previously attributed to the λ1 shell protein (12).

    • Translation of plant virus messenger rnas

      1979, Advances in Virus Research
    View all citing articles on Scopus
    View full text