Samuel E. Butcher
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View article: TDP-43 controls RNA structure through high affinity lattice interactions
TDP-43 controls RNA structure through high affinity lattice interactions Open
TDP-43 is an RNA binding protein implicated in neurodegenerative disease. TDP-43 binds to GU dinucleotide repeats, which are highly abundant sequences in human RNA. Here we show TDP- 43 has one of the highest affinities and specificities m…
View article: Sequence and ionic requirements of pUG fold quadruplexes
Sequence and ionic requirements of pUG fold quadruplexes Open
Poly(UG) or “pUG” repeat RNA can fold into a left-handed parallel quadruplex, the pUG fold. The pUG fold directs the amplification of RNAi in C. elegans , and pUG sequences are abundant in eukaryotic transcriptomes. Here, we report the seq…
View article: The structure, folding kinetics, and dynamics of long poly(UG) RNA
The structure, folding kinetics, and dynamics of long poly(UG) RNA Open
Long poly(UG) or “pUG” dinucleotide repeats are abundant in eukaryotic transcriptomes. Over a thousand human genes have pUGs longer than 24 repeats, including the cancer-associated lncRNA NEAT1. In C. elegans, enzymatic addition of long pU…
View article: The structure, folding kinetics and dynamics of long poly(UG) RNA
The structure, folding kinetics and dynamics of long poly(UG) RNA Open
Long poly(UG) or “pUG” dinucleotide repeats are abundant in eukaryotic transcriptomes. Thousands of human genes have pUGs longer than 24 repeats, including the cancer-associated lncRNA NEAT1. In C. elegans , enzymatic addition of long pUGs…
View article: A novel L-RNA aptamer to regulate the pUG fold RNA-induced gene expression <i>in vivo</i>
A novel L-RNA aptamer to regulate the pUG fold RNA-induced gene expression <i>in vivo</i> Open
G-quadruplex (G4) is a guanine-rich secondary structure found in DNA and RNA involved in various biological roles. Recently, a non-canonical RNA G-quadruplex (rG4), known as poly(UG) (pUG) fold, was discovered in Caenorhabditis elegans. Th…
View article: RNA Modifications and Prp24 Coordinate Lsm2-8 Binding Dynamics during <i>S. cerevisiae</i> U6 snRNP Assembly
RNA Modifications and Prp24 Coordinate Lsm2-8 Binding Dynamics during <i>S. cerevisiae</i> U6 snRNP Assembly Open
In eukaryotes, the process of intron removal from nuclear pre-mRNA is performed by the spliceosome, a dynamic molecular machine composed of small nuclear ribonucleoproteins (snRNPs; U1, U2, U4, U5, and U6) and dozens of other protein splic…
View article: Self-assembly and condensation of intermolecular poly(UG) RNA quadruplexes
Self-assembly and condensation of intermolecular poly(UG) RNA quadruplexes Open
Poly(UG) or ‘pUG’ dinucleotide repeats are highly abundant sequences in eukaryotic RNAs. In Caenorhabditis elegans, pUGs are added to RNA 3′ ends to direct gene silencing within Mutator foci, a germ granule condensate. Here, we show that p…
View article: Perturbing HIV-1 Ribosomal Frameshifting Frequency Reveals a cis Preference for Gag-Pol Incorporation into Assembling Virions
Perturbing HIV-1 Ribosomal Frameshifting Frequency Reveals a cis Preference for Gag-Pol Incorporation into Assembling Virions Open
HIV-1 virion production is driven by Gag and Gag-Pol (GP) proteins, with Gag forming the bulk of the capsid and driving budding, while GP binds Gag to deliver the essential virion enzymes protease, reverse transcriptase, and integrase. Vir…
View article: Inhibition of Nonsense-Mediated Decay Induces Nociceptive Sensitization through Activation of the Integrated Stress Response
Inhibition of Nonsense-Mediated Decay Induces Nociceptive Sensitization through Activation of the Integrated Stress Response Open
RNA stability is meticulously controlled. Here, we sought to determine whether an essential post-transcriptional regulatory mechanism plays a role in pain. Nonsense-mediated decay (NMD) safeguards against translation of mRNAs that harbor p…
View article: Identification of transient intermediates during spliceosome activation by single molecule fluorescence microscopy
Identification of transient intermediates during spliceosome activation by single molecule fluorescence microscopy Open
Spliceosome activation is the process of creating the catalytic site for RNA splicing and occurs de novo on each intron following spliceosome assembly. Dozens of factors bind to or are released from the activating spliceosome including the…
View article: Identification of transient intermediates during spliceosome activation by single molecule fluorescence microscopy
Identification of transient intermediates during spliceosome activation by single molecule fluorescence microscopy Open
Spliceosome activation is the process of creating the catalytic site for RNA splicing and occurs de novo on each intron following spliceosome assembly. Dozens of factors bind to or are released from the activating spliceosome including the…
View article: Identification of Transient Intermediates During Spliceosome Activation by Single Molecule Fluorescence Microscopy
Identification of Transient Intermediates During Spliceosome Activation by Single Molecule Fluorescence Microscopy Open
Summary Spliceosome activation is the process of creating the catalytic site for RNA splicing and occurs de novo on each intron following spliceosome assembly. Dozens of factors bind to or are released from the activating spliceosome inclu…
View article: An Atypical RNA Quadruplex Marks RNAs as Vectors for Gene Silencing
An Atypical RNA Quadruplex Marks RNAs as Vectors for Gene Silencing Open
The addition of poly(UG) ("pUG") repeats to 3' termini of mRNAs drives gene silencing and trans-generational epigenetic inheritance in the metazoan C. elegans. pUG tails promote silencing by recruiting an RNA-dependent RNA Polymerase (RdRP…
View article: Dynamic Motions of the HIV-1 Frameshift Site RNA
Dynamic Motions of the HIV-1 Frameshift Site RNA Open
The HIV-1 frameshift site (FS) plays a critical role in viral replication. During translation, the HIV-1 FS transitions from a 3-helix to a 2-helix junction RNA secondary structure. The 2-helix junction structure contains a GGA bulge, and …
View article: Structure and Dynamics of the HIV-1 Frameshift Element RNA
Structure and Dynamics of the HIV-1 Frameshift Element RNA Open
The HIV-1 ribosomal frameshift element is highly structured, regulates translation of all virally encoded enzymes, and is a promising therapeutic target. The prior model for this motif contains two helices separated by a three-nucleotide b…
View article: Expanded DNA and RNA Trinucleotide Repeats in Myotonic Dystrophy Type 1 Select Their Own Multitarget, Sequence-Selective Inhibitors
Expanded DNA and RNA Trinucleotide Repeats in Myotonic Dystrophy Type 1 Select Their Own Multitarget, Sequence-Selective Inhibitors Open
There are few methods available for the rapid discovery of multitarget drugs. Herein, we describe the template-assisted, target-guided discovery of small molecules that recognize d(CTG) in the expanded d(CTG·CAG) sequence and its r(CUG) tr…
View article: Molecular basis for the distinct cellular functions of the Lsm1-7 and Lsm2-8 complexes
Molecular basis for the distinct cellular functions of the Lsm1-7 and Lsm2-8 complexes Open
Eukaryotes possess eight highly conserved Lsm (like Sm) proteins that assemble into circular, heteroheptameric complexes, bind RNA, and direct a diverse range of biological processes. Among the many essential functions of Lsm proteins, the…
View article: Structural basis for the evolution of cyclic phosphodiesterase activity in the U6 snRNA exoribonuclease Usb1
Structural basis for the evolution of cyclic phosphodiesterase activity in the U6 snRNA exoribonuclease Usb1 Open
U6 snRNA undergoes post-transcriptional 3′ end modification prior to incorporation into the active site of spliceosomes. The responsible exoribonuclease is Usb1, which removes nucleotides from the 3′ end of U6 and, in humans, leaves a 2′,3…
View article: Structure of an RNA helix with pyrimidine mismatches and cross-strand stacking
Structure of an RNA helix with pyrimidine mismatches and cross-strand stacking Open
The structure of a 22-base-pair RNA helix with mismatched pyrimidine base pairs is reported. The helix contains two symmetry-related CUG sequences: a triplet-repeat motif implicated in myotonic dystrophy type 1. The CUG repeat contains a U…
View article: Conformational flexibility in the enterovirus RNA replication platform
Conformational flexibility in the enterovirus RNA replication platform Open
A presumed RNA cloverleaf (5′CL), located at the 5′-most end of the noncoding region of the enterovirus genome, is the primary established site for initiation of genomic replication. Stem–loop B (SLB) and stem–loop D (SLD), the two largest…
View article: Structural and mechanistic basis for preferential deadenylation of U6 snRNA by Usb1
Structural and mechanistic basis for preferential deadenylation of U6 snRNA by Usb1 Open
Post-transcriptional modification of snRNA is central to spliceosome function. Usb1 is an exoribonuclease that shortens the oligo-uridine tail of U6 snRNA, resulting in a terminal 2',3' cyclic phosphate group in most eukaryotes, including …
View article: Architecture of the U6 snRNP reveals specific recognition of 3′-end processed U6 snRNA
Architecture of the U6 snRNP reveals specific recognition of 3′-end processed U6 snRNA Open
The spliceosome removes introns from precursor messenger RNA (pre-mRNA) to produce mature mRNA. Prior to catalysis, spliceosomes are assembled de novo onto pre-mRNA substrates. During this assembly process, U6 small nuclear RNA (snRNA) und…
View article: The life of U6 small nuclear RNA, from cradle to grave
The life of U6 small nuclear RNA, from cradle to grave Open
Removal of introns from precursor messenger RNA (pre-mRNA) and some noncoding transcripts is an essential step in eukaryotic gene expression. In the nucleus, this process of RNA splicing is carried out by the spliceosome, a multi-megaDalto…