The resolution revolution of cryo-electron microscopy (cryo-EM) has made a significant impact on the structural analysis of the Pneumoviridae multifunctional RNA polymerases. In recent months, several high-resolution structures of apo RNA polymerases of Pneumoviridae, which includes the human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV), have been determined by single-particle cryo-EM. These structures illustrated high similarities and minor differences between the Pneumoviridae polymerases and revealed the potential mechanisms of the Pneumoviridae RNA synthesis.
Get full access to this article
View all access options for this article.
References
1.
AbrahamG, and BanerjeeAK. Sequential transcription of the genes of vesicular stomatitis virus. Proc Natl Acad Sci U S A, 1976; 73:1504–1508.
2.
AfonsoCL, AmarasingheGK, BányaiK, et al.Taxonomy of the order Mononegavirales: update 2016. Arch Virol, 2016; 161:2351–2360.
3.
BallLA, and WhiteCN. Order of transcription of genes of vesicular stomatitis virus. Proc Natl Acad Sci U S A, 1976; 73:442–446.
4.
BalboPB, and BohmA. Mechanism of poly(A) polymerase: structure of the enzyme-MgATP-RNA ternary complex and kinetic analysis. Structure, 2007; 15:1117–1131.
5.
BienrothS, KellerW, and WahleE. Assembly of a processive messenger RNA polyadenylation complex. EMBO J, 1993; 12:585–594.
6.
CaoD, GaoY, RoeslerC, et al.Cryo-EM structure of the respiratory syncytial virus RNA polymerase. Nat Commun, 2020; 11:368.
7.
ChengY. Single-particle cryo-EM-How did it get here and where will it go. Science, 2018; 361:876–880.
8.
ChengY, GlaeserRM, and NogalesE. How cryo-EM became so hot. Cell, 2017; 171:1229–1231.
9.
ConzelmannKK. Nonsegmented negative-strand RNA viruses: genetics and manipulation of viral genomes. Annu Rev Genet, 1998; 32:123–162.
10.
CowlingVH. Regulation of mRNA cap methylation. Biochem J, 2009; 425:295–302.
11.
CramerP, BushnellDA, and KornbergRD. Structural basis of transcription: RNA polymerase II at 2.8 angstrom resolution. Science, 2001; 292:1863–1876.
12.
CuiR, WangY, WangL, et al.Cyclopiazonic acid, an inhibitor of calcium-dependent ATPases with antiviral activity against human respiratory syncytial virus. Antiviral Res, 2016; 132:38–45.
13.
DeffrasnesC, HamelinME, PrinceGA, and BoivinG. Identification and evaluation of a highly effective fusion inhibitor for human metapneumovirus. Antimicrob Agents Chemother, 2008; 52:279–287.
14.
EarlLA, FalconieriV, MilneJL, and SubramaniamS. Cryo-EM: beyond the microscope. Curr Opin Struct Biol, 2017; 46:71–78.
15.
FabregaC, HausmannS, ShenV, ShumanS, and LimaCD. Structure and mechanism of mRNA cap (guanine-N7) methyltransferase. Mol Cell, 2004; 13:77–89.
16.
FearnsR, CollinsPL, and PeeplesME. Functional analysis of the genomic and antigenomic promoters of human respiratory syncytial virus. J Virol, 2000; 74:6006–6014.
17.
FearnsR, PeeplesME, and CollinsPL. Increased expression of the N protein of respiratory syncytial virus stimulates minigenome replication but does not alter the balance between the synthesis of mRNA and antigenome. Virology, 1997; 236:188–201.
18.
FeuilletF, LinaB, Rosa-CalatravaM, and BoivinG. Ten years of human metapneumovirus research. J Clin Virol, 2012; 53:97–105.
19.
GilmanMSA, LiuC, FungA, et al.Structure of the respiratory syncytial virus polymerase complex. Cell, 2019; 179:193.e14–204.e14.
20.
GnattAL, CramerP, FuJ, et al.Structural basis of transcription: an RNA polymerase II elongation complex at 3.3 A resolution. Science, 2001; 292:1876–1882.
21.
HoCK, SriskandaV, McCrackenS, et al.The guanylyltransferase domain of mammalian mRNA capping enzyme binds to the phosphorylated carboxyl-terminal domain of RNA polymerase II. J Biol Chem, 1998; 273:9577–9585.
22.
HorwitzJA, JenniS, HarrisonSC, and WhelanSPJ. Structure of a rabies virus polymerase complex from electron cryo-microscopy. Proc Natl Acad Sci U S A, 2020; 117:2099–2107.
23.
JenniS, BloyetLM, Diaz-AvalosR, et al.Structure of the vesicular stomatitis virus L protein in complex with its phosphoprotein cofactor. Cell Rep, 2020; 30:53.e5–60.e5.
24.
KimHJ, JeongSH, HeoJH, et al.mRNA capping enzyme activity is coupled to an early transcription elongation. Mol Cell Biol, 2004; 24:6184–6193.
25.
KuoL, FearnsR, and CollinsPL. The structurally diverse intergenic regions of respiratory syncytial virus do not modulate sequential transcription by a dicistronic minigenome. J Virol, 1996; 70:6143–6150.
26.
KuoL, FearnsR, and CollinsPL. Analysis of the gene start and gene end signals of human respiratory syncytial virus: quasi-templated initiation at position 1 of the encoded mRNA. J Virol, 1997; 71:4944–4953.
27.
KuoL, GrosfeldH, CristinaJ, et al.Effects of mutations in the gene-start and gene-end sequence motifs on transcription of monocistronic and dicistronic minigenomes of respiratory syncytial virus. J Virol, 1996; 70:6892–6901.
28.
LiY, ReevesRM, WangX, et al.Global patterns in monthly activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus: a systematic analysis. Lancet Glob Health, 2019; 7:e1031–e1045.
29.
LiangB, LiZ, JenniS, et al.Structure of the L protein of vesicular stomatitis virus from electron cryomicroscopy. Cell, 2015; 162:314–327.
30.
MaesP, AmarasingheGK, AyllónMA, et al.Taxonomy of the order Mononegavirales: second update 2018. Arch Virol, 2019; 164:1233–1244.
31.
MandalSS, ChuC, WadaT, et al.Functional interactions of RNA-capping enzyme with factors that positively and negatively regulate promoter escape by RNA polymerase II. Proc Natl Acad Sci U S A, 2004; 101:7572–7577.
32.
MinkMA, StecDS, and CollinsPL. Nucleotide sequences of the 3′ leader and 5′ trailer regions of human respiratory syncytial virus genomic RNA. Virology, 1991; 185:615–624.
33.
OginoT, and GreenTJ. RNA Synthesis and capping by non-segmented negative strand RNA viral polymerases: lessons from a prototypic virus. Front Microbiol, 2019; 10:1490.
34.
PaganI, HolmesEC, and Simon-LoriereE. Level of gene expression is a major determinant of protein evolution in the viral order Mononegavirales. J Virol, 2012; 86:5253–5263.
35.
PanJ, QianX, LattmannS, et al.Structure of the human metapneumovirus polymerase phosphoprotein complex. Nature, 2020; 577:275–279.
36.
PiedraFA, QiuX, TengMN, et al.Non-gradient and genotype-dependent patterns of RSV gene expression. PLoS One, 2020; 15:e0227558.
37.
ProudfootNJ, FurgerA, and DyeMJ. Integrating mRNA processing with transcription. Cell, 2002; 108:501–512.
38.
RaunserS. Cryo-EM revolutionizes the structure determination of biomolecules. Angew Chem Int Ed Engl, 2017; 56:16450–16452.
39.
RenaudJP, ChariA, CiferriC, et al.Cryo-EM in drug discovery: achievements, limitations and prospects. Nat Rev Drug Discov, 2018; 17:471–492.
40.
RiveraCA, GómezRS, DíazRA, et al.Novel therapies and vaccines against the human respiratory syncytial virus. Expert Opin Investig Drugs, 2015; 24:1613–1630.
41.
Rivera-CalzadaA, and CarroniM. Editorial: technical advances in Cryo-electron microscopy. Front Mol Biosci, 2019; 6:72.
42.
ShahDP, ShahPK, AzziJM, et al.Human metapneumovirus infections in hematopoietic cell transplant recipients and hematologic malignancy patients: a systematic review. Cancer Lett, 2016; 379:100–106.
43.
ShenPS. The 2017 Nobel Prize in Chemistry: cryo-EM comes of age. Anal Bioanal Chem, 2018; 410:2053–2057.
44.
ShiT, McAllisterDA, O'BrienKL, et al.Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Lancet, 2017; 390:946–958.
45.
WhelanSP, BarrJN, and WertzGW. Transcription and replication of nonsegmented negative-strand RNA viruses. Curr Top Microbiol Immunol, 2004; 283:61–119.
