Precursor mRNA
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YTHDC1 mediates nuclear export of N6-methyladenosine methylated mRNAs Open
N6-methyladenosine (m6A) is the most abundant internal modification of eukaryotic messenger RNA (mRNA) and plays critical roles in RNA biology. The function of this modification is mediated by m6A-selective ‘reader’ proteins of the YTH fam…
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N 6-methyladenosine alters RNA structure to regulate binding of a low-complexity protein Open
N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic messenger RNA (mRNA), and affects almost every stage of the mRNA life cycle. The YTH-domain proteins can specifically recognize m6A modification to control m…
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m<sup>6</sup>A mRNA modifications are deposited in nascent pre-mRNA and are not required for splicing but do specify cytoplasmic turnover Open
Understanding the biologic role of N 6 -methyladenosine (m 6 A) RNA modifications in mRNA requires an understanding of when and where in the life of a pre-mRNA transcript the modifications are made. We found that HeLa cell chromatin-associ…
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N6-methyladenosine demethylase FTO targets pre-mRNAs and regulates alternative splicing and 3′-end processing Open
N6-methyladenosine (m6A) is the most abundant base modification found in messenger RNAs (mRNAs). The discovery of FTO as the first m6A mRNA demethylase established the concept of reversible RNA modification. Here, we present a comprehensiv…
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SR proteins are NXF1 adaptors that link alternative RNA processing to mRNA export Open
Nuclear export factor 1 (NXF1) exports mRNA to the cytoplasm after recruitment to mRNA by specific adaptor proteins. How and why cells use numerous different export adaptors is poorly understood. Here we critically evaluate members of the …
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The Dengue Virus NS5 Protein Intrudes in the Cellular Spliceosome and Modulates Splicing Open
Dengue virus NS5 protein plays multiple functions in the cytoplasm of infected cells, enabling viral RNA replication and counteracting host antiviral responses. Here, we demonstrate a novel function of NS5 in the nucleus where it interfere…
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Molecular Mechanisms of pre-mRNA Splicing through Structural Biology of the Spliceosome Open
Precursor messenger RNA (pre-mRNA) splicing is executed by the spliceosome. In the past 3 years, cryoelectron microscopy (cryo-EM) structures have been elucidated for a majority of the yeast spliceosomal complexes and for a few human splic…
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Stem–loop RNA labeling can affect nuclear and cytoplasmic mRNA processing Open
The binding of sequence-specific RNA-interacting proteins, such as the bacteriophage MS2 or PP7 coat proteins, to their corresponding target sequences has been extremely useful and widely used to visualize single mRNAs in vivo . However, i…
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Most human introns are recognized via multiple and tissue-specific branchpoints Open
Although branchpoint recognition is an essential component of intron excision during the RNA splicing process, the branchpoint itself is frequently assumed to be a basal, rather than regulatory, sequence feature. However, this assumption h…
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Structure of an active human histone pre-mRNA 3′-end processing machinery Open
Architecture of an mRNA processor The 3′-end processing of the three major classes of RNA polymerase II transcripts in metazoan cells—polyadenylated messenger RNAs (mRNAs), histone mRNAs, and small nuclear RNAs (snRNAs)—requires three dist…
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METTL4 catalyzes m6Am methylation in U2 snRNA to regulate pre-mRNA splicing Open
N 6-methylation of 2′-O-methyladenosine (Am) in RNA occurs in eukaryotic cells to generate N6,2′-O-dimethyladenosine (m6Am). Identification of the methyltransferase responsible for m6Am catalysis has accelerated studies on the function of …
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Spliceosomal snRNA Epitranscriptomics Open
Small nuclear RNAs (snRNAs) are critical components of the spliceosome that catalyze the splicing of pre-mRNA. snRNAs are each complexed with many proteins to form RNA-protein complexes, termed as small nuclear ribonucleoproteins (snRNPs),…
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The cryo-EM structure of the SF3b spliceosome complex bound to a splicing modulator reveals a pre-mRNA substrate competitive mechanism of action Open
Somatic mutations in spliceosome proteins lead to dysregulated RNA splicing and are observed in a variety of cancers. These genetic aberrations may offer a potential intervention point for targeted therapeutics. SF3B1, part of the U2 small…
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The Interchromatin Compartment Participates in the Structural and Functional Organization of the Cell Nucleus Open
This article focuses on the role of the interchromatin compartment (IC) in shaping nuclear landscapes. The IC is connected with nuclear pore complexes (NPCs) and harbors splicing speckles and nuclear bodies. It is postulated that the IC pr…
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A Day in the Life of the Exon Junction Complex Open
The exon junction complex (EJC) is an abundant messenger ribonucleoprotein (mRNP) component that is assembled during splicing and binds to mRNAs upstream of exon-exon junctions. EJCs accompany the mRNA during its entire life in the nucleus…
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Interchangeable SF3B1 inhibitors interfere with pre-mRNA splicing at multiple stages Open
The protein SF3B1 is a core component of the spliceosome, the large ribonucleoprotein complex responsible for pre-mRNA splicing. Interest in SF3B1 intensified when tumor exome sequencing revealed frequent specific SF3B1 mutations in a vari…
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3′-End Processing of Eukaryotic mRNA: Machinery, Regulation, and Impact on Gene Expression Open
Formation of the 3′ end of a eukaryotic mRNA is a key step in the production of a mature transcript. This process is mediated by a number of protein factors that cleave the pre-mRNA, add a poly(A) tail, and regulate transcription by protei…
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Cajal body function in genome organization and transcriptome diversity Open
Nuclear bodies contribute to non‐random organization of the human genome and nuclear function. Using a major prototypical nuclear body, the Cajal body, as an example, we suggest that these structures assemble at specific gene loci located …
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Pre-mRNA processing includes <i>N</i><sup>6</sup> methylation of adenosine residues that are retained in mRNA exons and the fallacy of “RNA epigenetics” Open
By using a cell fraction technique that separates chromatin-associated nascent RNA, newly completed nucleoplasmic mRNA and cytoplasmic mRNA, we have shown in a previous study that residues in exons are methylated (m 6 A) in nascent pre-mRN…
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AtU2<span>AF</span>65b functions in abscisic acid mediated flowering via regulating the precursor messenger <span>RNA</span> splicing of <i><span>ABI</span>5</i> and <i><span>FLC</span></i> in <i>Arabidopsis</i> Open
Summary In mammalians and yeast, the splicing factor U2 AF 65/Mud2p functions in precursor messenger RNA (pre‐ mRNA ) processing. Arabidopsis AtU2 AF 65b encodes a putative U2 AF 65 but its specific functions in plants are unknown. This pa…
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Structural and functional modularity of the U2 snRNP in pre-mRNA splicing Open
The U2 small nuclear ribonucleoprotein (snRNP) is an essential component of the spliceosome, the cellular machine responsible for removing introns from precursor mRNAs (pre-mRNAs) in all eukaryotes. U2 is an extraordinarily dynamic splicin…
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Global analysis of pre-mRNA subcellular localization following splicing inhibition by spliceostatin A Open
Spliceostatin A (SSA) is a methyl ketal derivative of FR901464, a potent antitumor compound isolated from a culture broth of Pseudomonas sp . no. 2663. These compounds selectively bind to the essential spliceosome component SF3b, a subcomp…
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Coordinate regulation of alternative pre-mRNA splicing events by the human RNA chaperone proteins hnRNPA1 and DDX5 Open
Alternative premessenger RNA (pre-mRNA) splicing is a post-transcriptional mechanism for controlling gene expression. Splicing patterns are determined by both RNA-binding proteins and nuclear pre-mRNA structure. Here, we analyzed pre-mRNA …
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The trypanocidal benzoxaborole AN7973 inhibits trypanosome mRNA processing Open
Kinetoplastid parasites-trypanosomes and leishmanias-infect millions of humans and cause economically devastating diseases of livestock, and the few existing drugs have serious deficiencies. Benzoxaborole-based compounds are very promising…
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Specific G-quadruplex ligands modulate the alternative splicing of Bcl-X Open
Sequences with the potential to form RNA G-quadruplexes (G4s) are common in mammalian introns, especially in the proximity of the 5' splice site (5'SS). However, the difficulty of demonstrating that G4s form in pre-mRNA in functional condi…
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The YTHDF proteins ECT2 and ECT3 bind largely overlapping target sets and influence target mRNA abundance, not alternative polyadenylation Open
Gene regulation via N6 -methyladenosine (m 6 A) in mRNA involves RNA-binding proteins that recognize m 6 A via a YT521-B homology (YTH) domain. The plant YTH domain proteins ECT2 and ECT3 act genetically redundantly in stimulating cell pro…
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CircRNA—Protein Interactions in Muscle Development and Diseases Open
Circular RNA (circRNA) is a kind of novel endogenous noncoding RNA formed through back-splicing of mRNA precursor. The biogenesis, degradation, nucleus–cytoplasm transport, location, and even translation of circRNA are controlled by RNA-bi…
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Transcriptome-wide splicing network reveals specialized regulatory functions of the core spliceosome Open
The spliceosome is the complex molecular machinery that sequentially assembles on eukaryotic messenger RNA precursors to remove introns (pre-mRNA splicing), a physiologically regulated process altered in numerous pathologies. We report tra…
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hnRNP A1/A2 and Sam68 collaborate with SRSF10 to control the alternative splicing response to oxaliplatin-mediated DNA damage Open
Little is known about how RNA binding proteins cooperate to control splicing, and how stress pathways reconfigure these assemblies to alter splice site selection. We have shown previously that SRSF10 plays an important role in the Bcl-x sp…
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Molecular Mechanism and Evolution of Nuclear Pre-mRNA and Group II Intron Splicing: Insights from Cryo-Electron Microscopy Structures Open
Nuclear pre-mRNA splicing and group II intron self-splicing both proceed by two-step transesterification reactions via a lariat intron intermediate. Recently determined cryo-electron microscopy (cryo-EM) structures of catalytically active …