A5025658481- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Cancer-related molecular mechanisms research
- HVDC Systems and Fault Protection
- Peptidase Inhibition and Analysis
- Cancer-related gene regulation
- Electron Spin Resonance Studies
- Biochemical effects in animals
- interferon and immune responses
- Computational Drug Discovery Methods
- RNA Research and Splicing
- Receptor Mechanisms and Signaling
- Respiratory viral infections research
- SARS-CoV-2 and COVID-19 Research
- Crystallization and Solubility Studies
- RNA Interference and Gene Delivery
- Pneumocystis jirovecii pneumonia detection and treatment
- S100 Proteins and Annexins
- X-ray Diffraction in Crystallography
- Epigenetics and DNA Methylation
- Bacteriophages and microbial interactions
- Viral Infections and Immunology Research
- Signaling Pathways in Disease
The University of Texas Health Science Center at San Antonio
2020-2025
The University of Texas at San Antonio
2020-2022
Cancer Research Institute of the Slovak Academy of Sciences
2020
Abstract The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19 illness, has caused millions infections worldwide. In SARS coronaviruses, non-structural protein 16 (nsp16), in conjunction with nsp10, methylates 5′-end virally encoded mRNAs to mimic cellular mRNAs, thus protecting virus from host innate immune restriction. We report here high-resolution structure a ternary complex SARS-CoV-2 nsp16 and nsp10 presence cognate RNA substrate analogue...
Methyltransferase like-3 (METTL3) and METTL14 complex transfers a methyl group from S-adenosyl-L-methionine to N6 amino of adenosine bases in RNA (m6A) DNA (m6dA). Emerging evidence highlights role METTL3-METTL14 the chromatin context, especially processes where are held close proximity. However, mechanistic framework about specificity for substrate RNA/DNA their interrelationship remain unclear. By systematically studying methylation activity binding affinity number oligos with different...
Abstract The SARS-CoV-2 nsp16/nsp10 enzyme complex modifies the 2′-OH of first transcribed nucleotide viral mRNA by covalently attaching a methyl group to it. 2′- O methylation converts status cap from Cap-0 Cap-1, and thus, helps virus evade immune surveillance in host cells. Here, we report two structures representing pre- post-release states RNA product (Cap-1). We observe overall widening upon formation, an inward twisting motion substrate binding region release. These conformational...
The nuclear METTL3-METTL14 transfers a methyl group from SAM to convert the N 6 of adenosine (A) in RNA m A and ssDNA 6mA. marks are prevalent eukaryotic mRNAs lncRNAs modulate their stability fate context-dependent manner. cytoplasmic METTL3 can act as reader. However, precise mechanism during m6A writing, reading, or sensing is unclear. Here, we present ~2.5 Å structure methyltransferase core human complex with reaction product mimic, -methyladenosine monophosphate (m A), representing...
The nuclear METTL3-METTL14 transfers a methyl group from SAM to convert the N 6 of adenosine (A) in RNA m A and ssDNA 6mA. marks are prevalent eukaryotic mRNAs lncRNAs modulate their stability fate context-dependent manner. cytoplasmic METTL3 can act as reader. However, precise mechanism during m6A writing, reading, or sensing is unclear. Here, we present ~2.5 Å structure methyltransferase core human complex with reaction product mimic, -methyladenosine monophosphate (m A), representing...
2'-O-ribose methylation of the first transcribed base (adenine or A1 in SARS-CoV-2) viral RNA mimics host RNAs and subverts innate immune response. How nsp16, with partner nsp10, assembles on 5'-end SARS-CoV-2 mRNA to methylate is not fully understood. We present a ∼2.4 Å crystal structure heterotetrameric complex formed by cooperative assembly two nsp16/nsp10 heterodimers one 10-mer Cap-1 (product) bound each. An aromatic zipper-like motif nsp16 N-terminal regions nsp10 orchestrate...
Abstract The novel severe acute respiratory syndrome coronoavirus-2 (SARS-CoV-2), the causative agent of COVID-19 illness, has caused over 2 million infections worldwide in four months. In SARS coronaviruses, non-structural protein 16 (nsp16) methylates 5’-end virally encoded mRNAs to mimic cellular mRNAs, thus protecting virus from host innate immune restriction. We report here high-resolution structure a ternary complex full-length nsp16 and nsp10 SARS-CoV-2 presence cognate RNA substrate...
<title>Abstract</title> The nuclear METTL3-METTL14 enzyme complex transfers a methyl group from S-adenosyl-L-methionine (SAM) to the <italic>N</italic><sup><italic>6</italic></sup> amino of an adenosine (A) base in RNA convert it m<sup>6</sup>A and ssDNA 6mA. marks are prevalent eukaryotic mRNAs lncRNAs modulate their stability fate context-dependent manner. cytoplasmic METTL3 can act as m6A reader regulate mRNA translation. However, precise mechanism that actuates switch writer...
<title>Abstract</title> The nuclear METTL3-METTL14 transfers a methyl group from SAM to convert the <italic>N</italic><sup><italic>6</italic></sup> of adenosine (A) in RNA m<sup>6</sup>A and ssDNA 6mA. marks are prevalent eukaryotic mRNAs lncRNAs modulate their stability fate context-dependent manner. cytoplasmic METTL3 can act as reader. However, precise mechanism during m6A writing, reading, or sensing is unclear. Here, we present ~2.5 Å structure methyltransferase core human complex with...
Abstract 2’- O -ribose methylation of the first transcribed base (adenine or A 1 in SARS-CoV-2) viral RNA mimics host RNAs and subverts innate immune response. How nsp16, with its obligate partner nsp10, assembles on 5’-end SARS-CoV-2 mRNA to methylate has not been fully understood. We present a ∼ 2.4 Å crystal structure heterotetrameric complex formed by cooperative assembly two nsp16/nsp10 heterodimers one 10-mer Cap-1 (product) bound each. An aromatic zipper-like motif nsp16 N-terminal...
Abstract The SARS-CoV-2 nsp16/nsp10 enzyme complex modifies the 2’-OH of first transcribed nucleotide viral mRNA by covalently attaching a methyl group to it. 2’- O methylation converts status cap from Cap-0 Cap-1, and thus, helps virus evade immune surveillance in host cell. Here, we report two structures representing pre- post-release states RNA product (Cap-1). We observe overall widening upon formation, an inward twisting motion substrate binding region release. These conformational...
Abstract Methyltransferase like-3 (METTL3) and METTL14 complex transfers a methyl group from S -adenosyl-L-methionine to N 6 amino of adenosine bases in RNA (m A) DNA dA). Emerging evidence highlights role METTL3-METTL14 the chromatin context, especially processes where are held close proximity. However, mechanistic framework about specificity for substrate RNA/DNA their interrelationship remain unclear. By systematically studying methylation activity binding affinity number oligos with...
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19 illness is responsible for more than half a million deaths in United States alone.The SARS-CoV-2 nsp16/nsp10 enzyme complex modifies 2'-OH first transcribed nucleotide (N1 base) viral mRNA by covalently attaching methyl group to it.This single RNA modification event converts status cap from Cap-0 ( m7 GpppA) Cap-1 GpppAm) and helps virus evade immune surveillance host cell.Here, we report three...