Getting to the end of RNA: structural analysis of protein recognition of 5' and 3' termini.

The specific recognition by proteins of the 5' and 3' ends of RNA molecules is an important facet of many cellular processes, including RNA maturation, regulation of translation initiation and control of gene expression by degradation and RNA interference. The aim of this review is to survey recent structural analyses of protein binding domains that specifically bind to the extreme 5' or 3' termini of RNA. For reasons of space and because their interactions are also governed by catalytic considerations, we have excluded enzymes that modify the 5' and 3' extremities of RNA. It is clear that there is enormous structural diversity among the proteins that have evolved to bind to the ends of RNA molecules. Moreover, they commonly exhibit conformational flexibility that appears to be important for binding and regulation of the interaction. This flexibility has sometimes complicated the interpretation of structural results and presents significant challenges for future investigations.

[1]  Niklas Henriksson,et al.  Structural basis of m(7)GpppG binding to poly(A)-specific ribonuclease. , 2009, Structure.

[2]  J. McCarthy,et al.  Stabilization of Eukaryotic Initiation Factor 4E Binding to the mRNA 5′-Cap by Domains of eIF4G* , 2000, The Journal of Biological Chemistry.

[3]  F A Quiocho,et al.  Structural basis for sequence-nonspecific recognition of 5'-capped mRNA by a cap-modifying enzyme. , 1998, Molecular cell.

[4]  K. Borden,et al.  Cap‐free structure of eIF4E suggests a basis for conformational regulation by its ligands , 2006, The EMBO journal.

[5]  Y. Tomari,et al.  Drosophila argonaute1 and argonaute2 employ distinct mechanisms for translational repression. , 2009, Molecular cell.

[6]  W. Scott,et al.  Structure of Escherichia coli RNase E catalytic domain and implications for RNA turnover , 2005, Nature.

[7]  S. Peltz,et al.  A novel mRNA‐decapping activity in HeLa cytoplasmic extracts is regulated by AU‐rich elements , 2001, The EMBO journal.

[8]  M. Walkinshaw,et al.  Crystallographic and mass spectrometric characterisation of eIF4E with N7-alkylated cap derivatives. , 2007, Journal of molecular biology.

[9]  P. Fechter,et al.  Recognition of mRNA cap structures by viral and cellular proteins. , 2005, The Journal of general virology.

[10]  Olivier Voinnet,et al.  Antiviral Immunity Directed by Small RNAs , 2007, Cell.

[11]  B. Luisi,et al.  Information available at cut rates: structure and mechanism of ribonucleases , 2006, Current Opinion in Structural Biology.

[12]  B. Simon,et al.  Structure and nucleic-acid binding of the Drosophila Argonaute 2 PAZ domain , 2003, Nature.

[13]  A. Gingras,et al.  Cap-dependent translation initiation in eukaryotes is regulated by a molecular mimic of eIF4G. , 1999, Molecular cell.

[14]  D. Patel,et al.  Structural basis for overhang-specific small interfering RNA recognition by the PAZ domain , 2004, Nature.

[15]  Y. Yuan,et al.  Structural basis for recognition and sequestration of UUU(OH) 3' temini of nascent RNA polymerase III transcripts by La, a rheumatic disease autoantigen. , 2006, Molecular cell.

[16]  D. J. Van Horn,et al.  The La protein in Schizosaccharomyces pombe: a conserved yet dispensable phosphoprotein that functions in tRNA maturation. , 1997, RNA.

[17]  Lisa N Kinch,et al.  The human Ago2 MC region does not contain an eIF4E-like mRNA cap binding motif , 2009, Biology Direct.

[18]  N. Sonenberg,et al.  Weak binding affinity of human 4EHP for mRNA cap analogs. , 2007, RNA.

[19]  Joe D. Lewis,et al.  The structural basis for cap binding by influenza virus polymerase subunit PB2 , 2008, Nature Structural &Molecular Biology.

[20]  L. Malinina,et al.  Recognition of small interfering RNA by a viral suppressor of RNA silencing , 2003, Nature.

[21]  Toshimasa Ishida,et al.  Structural basis for mRNA Cap-Binding regulation of eukaryotic initiation factor 4E by 4E-binding protein, studied by spectroscopic, X-ray crystal structural, and molecular dynamics simulation methods. , 2005, Biochimica et biophysica acta.

[22]  P. Zamore,et al.  Kinetic analysis of the RNAi enzyme complex , 2004, Nature Structural &Molecular Biology.

[23]  S Cusack,et al.  Crystal structure of the human nuclear cap binding complex. , 2001, Molecular cell.

[24]  G. Wagner,et al.  The mRNA cap-binding protein eIF4E in post-transcriptional gene expression , 2004, Nature Structural &Molecular Biology.

[25]  J. Clardy,et al.  Structural basis of m7GpppG binding to the nuclear cap-binding protein complex , 2002, Nature Structural Biology.

[26]  Thomas Tuschl,et al.  Structural basis for 5'-end-specific recognition of the guide RNA strand by the A. fulgidus PIWI protein , 2005 .

[27]  T. Cedervall,et al.  The La protein. , 2002, Annual review of biochemistry.

[28]  T. Tuschl,et al.  Structure of an argonaute silencing complex with a seed-containing guide DNA and target RNA duplex , 2008, Nature.

[29]  S. Cusack,et al.  Specificity of recognition of mRNA 5' cap by human nuclear cap-binding complex. , 2005, RNA.

[30]  D. Barford,et al.  Crystal structure of a PIWI protein suggests mechanisms for siRNA recognition and slicer activity , 2004, The EMBO journal.

[31]  M. M. Karim,et al.  Repressor binding to a dorsal regulatory site traps human eIF4E in a high cap‐affinity state , 1999, The EMBO journal.

[32]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[33]  J. Stȩpiński,et al.  A cap binding protein that may mediate nuclear export of RNA polymerase II-transcribed RNAs , 1992, The Journal of cell biology.

[34]  G. Scheper,et al.  Phosphorylation of Eukaryotic Initiation Factor 4E Markedly Reduces Its Affinity for Capped mRNA* , 2002, The Journal of Biological Chemistry.

[35]  G. Szittya,et al.  Size Selective Recognition of siRNA by an RNA Silencing Suppressor , 2003, Cell.

[36]  R. Rhoads,et al.  Kinetic Mechanism for Assembly of the m7GpppG·eIF4E·eIF4G Complex* , 2008, Journal of Biological Chemistry.

[37]  A. Hinnebusch,et al.  Regulation of Translation Initiation in Eukaryotes: Mechanisms and Biological Targets , 2009, Cell.

[38]  T. Tuschl,et al.  Crystal structure of A. aeolicus Argonaute provides unique perspectives into the mechanism of guide strand-mediated mRNA cleavage , 2005 .

[39]  M. Ohno,et al.  The evolutionarily conserved region of the U snRNA export mediator PHAX is a novel RNA-binding domain that is essential for U snRNA export. , 2001, RNA.

[40]  S. Wolin,et al.  The Yeast La Protein Is Required for the 3′ Endonucleolytic Cleavage That Matures tRNA Precursors , 1997, Cell.

[41]  John G Doench,et al.  Specificity of microRNA target selection in translational repression. , 2004, Genes & development.

[42]  T. Tuschl,et al.  Crystal structure of A. aeolicus argonaute, a site-specific DNA-guided endoribonuclease, provides insights into RISC-mediated mRNA cleavage. , 2005, Molecular cell.

[43]  Matthew T Miller,et al.  Basis of altered RNA-binding specificity by PUF proteins revealed by crystal structures of yeast Puf4p , 2008, Nature Structural &Molecular Biology.

[44]  D. Lane,et al.  Crystallization of eIF4E complexed with eIF4GI peptide and glycerol reveals distinct structural differences around the cap-binding site , 2009, Cell cycle.

[45]  M. Ehrenberg,et al.  The mRNA Cap Structure Stimulates Rate of Poly(A) Removal and Amplifies Processivity of Degradation* , 2001, The Journal of Biological Chemistry.

[46]  A. Gingras,et al.  Cocrystal Structure of the Messenger RNA 5′ Cap-Binding Protein (eIF4E) Bound to 7-methyl-GDP , 1997, Cell.

[47]  S. Curry,et al.  Structural analysis of cooperative RNA binding by the La motif and central RRM domain of human La protein , 2004, Nature Structural &Molecular Biology.

[48]  Phillip D Zamore,et al.  Perspective: machines for RNAi. , 2005, Genes & development.

[49]  F. Quiocho,et al.  Specific protein recognition of an mRNA cap through its alkylated base , 1997, Nature Structural Biology.

[50]  E. Izaurralde,et al.  GW182 interaction with Argonaute is essential for miRNA-mediated translational repression and mRNA decay , 2008, Nature Structural &Molecular Biology.

[51]  S. Cusack,et al.  Large‐scale induced fit recognition of an m7GpppG cap analogue by the human nuclear cap‐binding complex , 2002, The EMBO journal.

[52]  C. Arias,et al.  Rotavirus Nonstructural Protein NSP3 Is Not Required for Viral Protein Synthesis , 2006, Journal of Virology.

[53]  Rahul C. Deo,et al.  Recognition of the Rotavirus mRNA 3′ Consensus by an Asymmetric NSP3 Homodimer , 2002, Cell.

[54]  J. Doudna,et al.  A three-dimensional view of the molecular machinery of RNA interference , 2009, Nature.

[55]  T. Misteli,et al.  Aberrant nuclear trafficking of La protein leads to disordered processing of associated precursor tRNAs. , 2002, Molecular cell.

[56]  R. Ficner,et al.  Crystal structure of the RRM domain of poly(A)-specific ribonuclease reveals a novel m(7)G-cap-binding mode. , 2008, Journal of molecular biology.

[57]  M. Kiledjian,et al.  Tri- to be mono- for bacterial mRNA decay. , 2009, Structure.

[58]  N. Sonenberg,et al.  eIF4G Dramatically Enhances the Binding of eIF4E to the mRNA 5′-Cap Structure* , 1997, The Journal of Biological Chemistry.

[59]  Mitsuo Sekine,et al.  Snurportin1, an m3G‐cap‐specific nuclear import receptor with a novel domain structure , 1998, The EMBO journal.

[60]  T. Ishida,et al.  Analysis of the mRNA cap-binding ability of human eukaryotic initiation factor-4E by use of recombinant wild-type and mutant forms. , 1996, European journal of biochemistry.

[61]  A. Gingras,et al.  Cloning and Characterization of 4EHP, a Novel Mammalian eIF4E-related Cap-binding Protein* , 1998, The Journal of Biological Chemistry.

[62]  K. Browning,et al.  The Structure of Eukaryotic Translation Initiation Factor-4E from Wheat Reveals a Novel Disulfide Bond1[OA] , 2007, Plant Physiology.

[63]  M. Kiriakidou,et al.  An mRNA m7G Cap Binding-like Motif within Human Ago2 Represses Translation , 2007, Cell.

[64]  Michael Sattler,et al.  Nucleic acid 3′-end recognition by the Argonaute2 PAZ domain , 2004, Nature Structural &Molecular Biology.

[65]  Joe D. Lewis,et al.  A nuclear cap binding protein complex involved in pre-mRNA splicing , 1994, Cell.

[66]  F. Quiocho,et al.  Structural basis of mRNA cap recognition by proteins. , 2000, Current opinion in structural biology.

[67]  Ying Huang,et al.  Separate RNA-binding surfaces on the multifunctional La protein mediate distinguishable activities in tRNA maturation , 2006, Nature Structural &Molecular Biology.

[68]  Andrew A. McCarthy,et al.  The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit , 2009, Nature.

[69]  D. Barford,et al.  Enhancement of the Seed-Target Recognition Step in RNA Silencing by a PIWI/MID Domain Protein , 2009, Molecular cell.

[70]  T. Tuschl,et al.  Structure of the guide-strand-containing argonaute silencing complex , 2008, Nature.

[71]  L. Phan,et al.  Control of transfer RNA maturation by phosphorylation of the human La antigen on serine 366. , 2000, Molecular cell.

[72]  Amy R. Cameron,et al.  Characterization of mammalian eIF4E-family members. , 2004, European journal of biochemistry.

[73]  B. Moss,et al.  Cytoplasmic transcription system encoded by vaccinia virus. , 1991, The Journal of biological chemistry.

[74]  J. E. Stefano.  Purified lupus antigen la recognizes an oligouridylate stretch common to the 3′ termini of RNA polymerase III transcripts , 1984, Cell.

[75]  S. Cusack,et al.  Inhibition of mRNA Deadenylation by the Nuclear Cap Binding Complex (CBC)* , 2006, Journal of Biological Chemistry.

[76]  F A Quiocho,et al.  mRNA cap recognition: dominant role of enhanced stacking interactions between methylated bases and protein aromatic side chains. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[77]  R. Parker,et al.  Structural basis of dcp2 recognition and activation by dcp1. , 2008, Molecular cell.

[78]  Martin J. Simard,et al.  Argonaute proteins: key players in RNA silencing , 2008, Nature Reviews Molecular Cell Biology.

[79]  Olivier Voinnet,et al.  The diversity of RNA silencing pathways in plants. , 2006, Trends in genetics : TIG.

[80]  Y. Hayashizaki,et al.  The RRM domain of poly(A)-specific ribonuclease has a noncanonical binding site for mRNA cap analog recognition , 2008, Nucleic acids research.

[81]  Miss A.O. Penney.  (b) , 1974, The New Yale Book of Quotations.

[82]  R. Maraia,et al.  The La protein-RNA complex surfaces. , 2006, Molecular cell.

[83]  H. Čelešnik,et al.  Initiation of RNA decay in Escherichia coli by 5' pyrophosphate removal. , 2007, Molecular cell.

[84]  Michael Sattler,et al.  Novel modes of protein-RNA recognition in the RNAi pathway. , 2005, Current opinion in structural biology.

[85]  D. Rubinson,et al.  A La protein requirement for efficient pre‐tRNA folding , 2003, The EMBO journal.

[86]  D. Engelke,et al.  5′ Processing of tRNA Precursors Can Be Modulated by the Human La Antigen Phosphoprotein , 1998, Molecular and Cellular Biology.

[87]  S. Knapp,et al.  Structures of the human eIF4E homologous protein, h4EHP, in its m7GTP-bound and unliganded forms. , 2007, Journal of molecular biology.

[88]  E. Petfalski,et al.  Precursors to the U3 Small Nucleolar RNA Lack Small Nucleolar RNP Proteins but Are Stabilized by La Binding , 2000, Molecular and Cellular Biology.

[89]  R. Maraia,et al.  Precursor-product discrimination by La protein during tRNA metabolism , 2009, Nature Structural &Molecular Biology.

[90]  R. Maraia,et al.  Recognition of Nascent RNA by the Human La Antigen: Conserved and Divergent Features of Structure and Function , 2001, Molecular and Cellular Biology.

[91]  Karin M Reinisch,et al.  Structure of the La motif: a winged helix domain mediates RNA binding via a conserved aromatic patch , 2004, The EMBO journal.

[92]  G. Wagner,et al.  Ribosome Loading onto the mRNA Cap Is Driven by Conformational Coupling between eIF4G and eIF4E , 2003, Cell.

[93]  D. Rubinson,et al.  U snRNP assembly in yeast involves the La protein , 2000, The EMBO journal.

[94]  H. Čelešnik,et al.  The bacterial enzyme RppH triggers messenger RNA degradation by 5′ pyrophosphate removal , 2008, Nature.

[95]  T. Hall,et al.  Structure and function of argonaute proteins. , 2005, Structure.

[96]  Zihe Rao,et al.  Crystal structure of an avian influenza polymerase PAN reveals an endonuclease active site , 2009, Nature.

[97]  F. Quiocho,et al.  The 1.85 Å Structure of Vaccinia Protein VP39: A Bifunctional Enzyme That Participates in the Modification of Both mRNA Ends , 1996, Cell.

[98]  K. Tomoo,et al.  Research Communication , 1971, PS: Political Science & Politics.

[99]  C. Dominguez,et al.  The RNA recognition motif, a plastic RNA‐binding platform to regulate post‐transcriptional gene expression , 2005, The FEBS journal.

[100]  P. Cary,et al.  Structure of the C-terminal domain of human La protein reveals a novel RNA recognition motif coupled to a helical nuclear retention element. , 2003, Structure.

[101]  E. Sontheimer,et al.  Origins and Mechanisms of miRNAs and siRNAs , 2009, Cell.

[102]  N. Sonenberg,et al.  Requirement of RNA Binding of Mammalian Eukaryotic Translation Initiation Factor 4GI (eIF4GI) for Efficient Interaction of eIF4E with the mRNA Cap , 2008, Molecular and Cellular Biology.

[103]  R. Maraia,et al.  A carboxy-terminal basic region controls RNA polymerase III transcription factor activity of human La protein , 1997, Molecular and cellular biology.

[104]  A. Gingras,et al.  Structure of translation factor elF4E bound to m7GDP and interaction with 4E-binding protein , 1997, Nature Structural Biology.

[105]  J. Belasco,et al.  Catalytic activation of multimeric RNase E and RNase G by 5'-monophosphorylated RNA. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[106]  Chengqi Lin,et al.  Structural basis for RNA‐silencing suppression by Tomato aspermy virus protein 2b , 2008, EMBO reports.

[107]  C. Steegborn,et al.  Contributions of the Individual Domains in Human La Protein to Its RNA 3′-End Binding Activity* , 2001, The Journal of Biological Chemistry.

[108]  Thomas Tuschl,et al.  Structural basis for 5′-end-specific recognition of guide RNA by the A. fulgidus Piwi protein , 2005, Nature.

[109]  Ying Huang,et al.  Mutations in the RNA Polymerase III Subunit Rpc11p That Decrease RNA 3′ Cleavage Activity Increase 3′-Terminal Oligo(U) Length and La-Dependent tRNA Processing , 2005, Molecular and Cellular Biology.

[110]  Achim Dickmanns,et al.  Structural basis for m3G‐cap‐mediated nuclear import of spliceosomal UsnRNPs by snurportin1 , 2005, The EMBO journal.

[111]  D. Barford,et al.  Structural insights into mRNA recognition from a PIWI domain–siRNA guide complex , 2005, Nature.

[112]  Maria R. Conte,et al.  Structural Analysis Reveals Conformational Plasticity in the Recognition of RNA 3′ Ends by the Human La Protein , 2008, Structure.

[113]  Ji-Joon Song,et al.  The crystal structure of the Argonaute2 PAZ domain reveals an RNA binding motif in RNAi effector complexes , 2003, Nature Structural Biology.

[114]  E. Wahle,et al.  Cap‐dependent deadenylation of mRNA , 2000, The EMBO journal.

[115]  Anne-Claude Gingras,et al.  Biophysical studies of eIF4E cap-binding protein: recognition of mRNA 5' cap structure and synthetic fragments of eIF4G and 4E-BP1 proteins. , 2002, Journal of molecular biology.

[116]  E. Izaurralde,et al.  Getting to the Root of miRNA-Mediated Gene Silencing , 2008, Cell.

[117]  G. Hannon,et al.  Crystal Structure of Argonaute and Its Implications for RISC Slicer Activity , 2004, Science.

[118]  Takayuki Murata,et al.  MicroRNA Inhibition of Translation Initiation in Vitro by Targeting the Cap-Binding Complex eIF4F , 2007, Science.

[119]  R. Maraia,et al.  Conservation of a Masked Nuclear Export Activity of La Proteins and Its Effects on tRNA Maturation , 2007, Molecular and Cellular Biology.

[120]  T. Tomcsanyi,et al.  Processing enzyme ribonuclease E specifically cleaves RNA I. An inhibitor of primer formation in plasmid DNA synthesis. , 1985, Journal of molecular biology.