Research Topics
Genomes and Genes | Melissa J MooreSummaryAffiliation: University of Massachusetts Medical School Country: USA Publications
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Publications
Pre-mRNA processing reaches back to transcription and ahead to translationMelissa J Moore
Howard Hughes Medical Institute, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA
Cell 136:688-700. 2009..The connections of pre-mRNA processing to upstream events in transcription and downstream events, including translation and mRNA decay, are elaborate, extensive, and remarkably interwoven...
Mutational analysis of human eIF4AIII identifies regions necessary for exon junction complex formation and nonsense-mediated mRNA decayToshiharu Shibuya
Howard Hughes Medical Institute, Department of Biochemistry, MS009, Brandeis University, 415 South Street, Waltham, MA 02454, USA
RNA 12:360-74. 2006..Implications of these findings are discussed in the context of other recent results and a new structural model for human eIF4AIII based on the known crystal structure of Saccharomyces cerevisiae eIF4AI...
Ordered and dynamic assembly of single spliceosomesAaron A Hoskins
Department of Biochemistry and Molecular Pharmacology, Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA
Science 331:1289-95. 2011..This experimental strategy should prove widely useful for mechanistic analysis of other macromolecular machines in environments approaching the complexity of living cells...
Biochemical analysis of the EJC reveals two new factors and a stable tetrameric protein coreThomas Ø Tange
Howard Hughes Medical Institute, Department of Biochemistry, Brandeis University, Waltham, MA 02454, USA
RNA 11:1869-83. 2005..Using the same methodology, we further identified what appears to be the minimal stable EJC core, a heterotetrameric complex consisting of eIF4AIII, Magoh, Y14, and MLN51...
The EJC factor eIF4AIII modulates synaptic strength and neuronal protein expressionCorinna Giorgi
Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02454, USA
Cell 130:179-91. 2007....
The three-dimensional arcitecture of the EJC coreM Elizabeth Stroupe
Howard Hughes Medical Institute, Brandeis University, 415 South Street, Waltham, MA 02454, USA
J Mol Biol 360:743-9. 2006..Using known X-ray crystallographic structures and a model of three of the four components, we propose a model for complex assembly on RNA and explain how Y14:Magoh may influence eIF4AIII's RNA binding...
New insights into the spliceosome by single molecule fluorescence microscopyAaron A Hoskins
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St, Worcester, MA 01605, USA
Curr Opin Chem Biol 15:864-70. 2011..These methods complement ensemble measurements of splicing in vivo and in vitro to facilitate kinetic dissection of pre-mRNA splicing...
The ever-increasing complexities of the exon junction complexThomas Ø Tange
Howard Hughes Medical Institute, Department of Biochemistry, MS009, Brandeis University, 415 South Street, Waltham, Massachusetts 02454, USA
Curr Opin Cell Biol 16:279-84. 2004..It is now apparent that the means of connection is a set of proteins, collectively called the exon junction complex, which are deposited as a consequence of splicing upstream of mRNA exon-exon junctions...
A convergence of rRNA and mRNA quality control pathways revealed by mechanistic analysis of nonfunctional rRNA decaySarah E Cole
Howard Hughes Medical Institute, Department of Biochemistry, Brandeis University, Waltham, MA 02454, USA
Mol Cell 34:440-50. 2009..We propose that 18S NRD and NGD are different observable outcomes of the same initiating event: a ribosome stalled inappropriately at a sense codon during translation elongation...
The nuclear nurture and cytoplasmic nature of localized mRNPsCorinna Giorgi
Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02454, USA
Semin Cell Dev Biol 18:186-93. 2007..In this review we focus on nuclear-acquired RNA-binding proteins and complexes that participate in determining the journey of localized mRNAs...
How introns influence and enhance eukaryotic gene expressionHervé Le Hir
Howard Hughes Medical Institute, Department of Biochemistry, MS009 Brandeis University, Waltham, MA 02454, USA
Trends Biochem Sci 28:215-20. 2003..A rudimentary understanding of these effects can prove invaluable to researchers interested in optimizing transgene expression in eukaryotic systems...
Visualizing the splicing of single pre-mRNA molecules in whole cell extractDaniel J Crawford
Howard Hughes Medical Institute, Brandeis University, Waltham, Massachusetts 02453, USA
RNA 14:170-9. 2008..This work provides a powerful new approach for elucidating the mechanisms of spliceosome function and demonstrates the feasibility of utilizing TIRF microscopy for biochemical studies of single molecules in highly complex environments...
The biflavonoid isoginkgetin is a general inhibitor of Pre-mRNA splicingKristine O'Brien
Howard Hughes Medical Institute, Brandeis University, Waltham, Massachusetts 02454, USA
J Biol Chem 283:33147-54. 2008..Our results suggest that splicing inhibition is the mechanistic basis of the anti-tumor activity of isoginkgetin. Thus, pre-mRNA splicing inhibitors may represent a novel avenue for development of new anti-cancer agents...
Pre-mRNA splicing: awash in a sea of proteinsMelissa S Jurica
Howard Hughes Medical Institute, Department of Biochemistry, Brandeis University, 415 South Street, Waltham, MA 02454, USA
Mol Cell 12:5-14. 2003..Another recurring theme regards the dynamic nature of spliceosomal complexes, which may be even more intricate than previously thought...
Splicing enhances translation in mammalian cells: an additional function of the exon junction complexAjit Nott
Howard Hughes Medical Institute, Department of Biochemistry, Brandeis University, Waltham, MA 02454, USA
Genes Dev 18:210-22. 2004..Furthermore, the ability to stimulate translation when bound inside an open reading frame appears to be a general feature of factors required for NMD...
Nuclear RNA turnoverMelissa J Moore
Howard Hughes Medical Institute, Department of Biochemistry, Brandeis University, 415 South Street, Waltham, MA 02454, USA
Cell 108:431-4. 2002..In mammalian cells, significantly more RNA is turned over in the nucleus than in the cytoplasm. However, only recently have we begun to understand the mechanisms and regulation of nuclear RNA decay...
Association of ribosomal proteins with nascent transcripts in S. cerevisiaePatricia A Schroder
Howard Hughes Medical Institute, Department of Biochemistry, Brandeis University, Waltham, MA 02454-9110, USA
RNA 11:1521-9. 2005..However, our data clearly indicate that this binding is independent of transcript translatability, so is therefore not indicative of nuclear translation...
The cellular EJC interactome reveals higher-order mRNP structure and an EJC-SR protein nexusGuramrit Singh
Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA
Cell 151:750-64. 2012..Further, their protection of long mRNA stretches from nuclease digestion suggests that endogenous EJCs and SR proteins cooperate to promote mRNA packaging and compaction...
Single-molecule colocalization FRET evidence that spliceosome activation precedes stable approach of 5' splice site and branch siteDaniel J Crawford
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605
Proc Natl Acad Sci U S A 110:6783-8. 2013..Separation of the sites of chemistry until very late in the splicing pathway may be crucial for preventing splicing at incorrect sites...
eIF4AIII binds spliced mRNA in the exon junction complex and is essential for nonsense-mediated decayToshiharu Shibuya
Howard Hughes Medical Institute, Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02454, USA
Nat Struct Mol Biol 11:346-51. 2004..Finally, a model is proposed by which eIF4AIII represents a new functional class of DExH/D box proteins that act as RNA clamps or 'place holders' for the sequence-independent attachment of additional factors to RNAs...
A late-acting quality control process for mature eukaryotic rRNAsFrederick J LaRiviere
Howard Hughes Medical Institute, Brandeis University, Waltham, Massachusetts 02454, USA
Mol Cell 24:619-26. 2006..Thus, eukaryotes possess a quality-control mechanism, nonfunctional rRNA decay (NRD), capable of detecting and eliminating the rRNA component of mature ribosomes...
Capturing splicing complexes to study structure and mechanismMelissa S Jurica
Howard Hughes Medical Institute, Department of Biochemistry, Brandeis University, 415 South Street, Waltham, MA 02454, USA
Methods 28:336-45. 2002..In this paper, we describe the purification in detail and discuss additional methods for trapping and analyzing other splicing complexes...
Interactions between eIF4AI and its accessory factors eIF4B and eIF4HNadja Rozovsky
Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, Massachusetts 02453, USA
RNA 14:2136-48. 2008..Our findings mirror and expand on recent biochemical and structural data regarding the interaction of eIF4AI's close relative eIF4AIII with its accessory protein MLN51...
Three-dimensional structure of C complex spliceosomes by electron microscopyMelissa S Jurica
Howard Hughes Medical Institute, Rosenstiel Basic Medical Sciences Research Center, Department of Biochemistry, Brandeis University, 415 South Street, Waltham, Massachusetts 02454, USA
Nat Struct Mol Biol 11:265-9. 2004..The structure reveals a particle of dimensions 27 x 22 x 24 nm with a relatively open arrangement of three primary domains...
A quantitative analysis of intron effects on mammalian gene expressionAjit Nott
Howard Hughes Medical Institute, Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02454, USA
RNA 9:607-17. 2003..However, nucleocytoplasmic mRNA distribution and mRNA stability were largely unaffected. These findings were extended to two other introns in a TCR-beta minigene...
Effects of the U1C L13 mutation and temperature regulation of yeast commitment complex formationHansen Du
Howard Hughes Medical Institute, Department of Biology, Brandeis University, MS008, 415 South Street, Waltham, MA 02454, USA
Proc Natl Acad Sci U S A 101:14841-6. 2004..A model is proposed to account for the L13 results...
Spliceosome assembly and compositionArianne J Matlin
Howard Hughes Medical Institute, Department of Biochemistry, Brandeis University, Waltham, MA 02454, USA
Adv Exp Med Biol 623:14-35. 2007..We also review recent advances regarding similarities and differences between the in vivo and in vitro assembly pathways, as well as proofreading mechanisms contributing to the fidelity of splice site selection...
Introns in UTRs: Why we should stop ignoring themAlicia A Bicknell
Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA
Bioessays 34:1025-34. 2012..Nonetheless, recent findings indicate that 5'- and 3'-UTR intron status is of significant functional consequence for the regulation of mammalian genes. Therefore these features should be ignored no longer...
An Ancient Transcription Factor Initiates the Burst of piRNA Production during Early Meiosis in Mouse TestesXin Zhiguo Li
Department of Biochemistry and Molecular Pharmacology, Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA
Mol Cell 50:67-81. 2013..This regulatory circuit, which can be detected in rooster testes, likely predates the divergence of birds and mammals...
RNA events. No end to nonsenseMelissa J Moore
Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02454, USA
Science 298:370-1. 2002
5' exon interactions within the human spliceosome establish a framework for exon junction complex structure and assemblyVienna L Reichert
Howard Hughes Medical Institute, Department of Biochemistry, Brandeis University, Massachusetts 02454, USA
Genes Dev 16:2778-91. 2002..Upon exon ligation, association of RNPS1, UAP56, and SRm160 is destabilized. In contrast, REF/Aly, Y14, and Magoh remain stably bound to spliced mRNA, indicating that these three proteins are components of the EJC core...
Purification and characterization of native spliceosomes suitable for three-dimensional structural analysisMelissa S Jurica
Howard Hughes Medical Institute, Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02454, USA
RNA 8:426-39. 2002..These images represent an important first step toward attaining a comprehensive three-dimensional understanding of pre-mRNA splicing...
Research Grants
- Mammalian Pre-mRNA Splicing MechanismsMelissa Moore; Fiscal Year: 2007....
- EXON LIGATION--THE SPLICEOSOME AND GROUP 11 INTRONSMelissa Moore; Fiscal Year: 1999..Together, these experiments should allow direct comparison of active site structure, 3' splice site recognition and mechanisms of catalysis by the spliceosome and both group II and group I self-splicing introns. ..
- Mammalian Pre-mRNA Splicing MechanismsMelissa Moore; Fiscal Year: 2009..abstract_text> ..
