High-throughput quantitation of protein-RNA UV-crosslinking efficiencies as a predictive tool for high confidence identification of RNA binding proteins
RNA. 2024 Feb 29:rna.079848.123. doi: 10.1261/rna.079848.123. Online ahead of print.ABSTRACTUV-crosslinking has proven to be an invaluable tool for the identification of RNA-protein interactomes. The paucity of methods for distinguishing background from bona fide RNA-protein interactions however makes attribution of RNA binding function on UV-crosslinking alone challenging. To address this need, we previously reported an RNA binding protein (RBP) confidence scoring metric, (RCS), incorporating both signal-to-noise (S:N) and protein abundance determinations to distinguish high and low confidence candidate RBPs. Although RCS...
Source: RNA - February 29, 2024 Category: Genetics & Stem Cells Authors: Johncarlo Kristofich Christopher Nicchitta Source Type: research
A side-by-side comparison of peptide-delivered antisense antibiotics employing different nucleotide mimics
RNA. 2024 Feb 27:rna.079969.124. doi: 10.1261/rna.079969.124. Online ahead of print.ABSTRACTAntisense oligomer (ASO)-based antibiotics that target mRNAs of essential bacterial genes have great potential for counteracting antimicrobial resistance and for precision microbiome editing. To date, the development of such antisense antibiotics has primarily focused on using phosphorodiamidate morpholino (PMO) and peptide nucleic acid (PNA) backbones, largely ignoring the growing number of chemical modalities that have spurred the success of ASO-based human therapy. Here, we directly compare the activities of seven chemically dist...
Source: RNA - February 27, 2024 Category: Genetics & Stem Cells Authors: Chandradhish Ghosh Linda Popella V Dhamodharan Jakob Jung Julia Dietzsch Lars Barquist Claudia H öbartner J örg Vogel Source Type: research
A side-by-side comparison of peptide-delivered antisense antibiotics employing different nucleotide mimics
RNA. 2024 Feb 27:rna.079969.124. doi: 10.1261/rna.079969.124. Online ahead of print.ABSTRACTAntisense oligomer (ASO)-based antibiotics that target mRNAs of essential bacterial genes have great potential for counteracting antimicrobial resistance and for precision microbiome editing. To date, the development of such antisense antibiotics has primarily focused on using phosphorodiamidate morpholino (PMO) and peptide nucleic acid (PNA) backbones, largely ignoring the growing number of chemical modalities that have spurred the success of ASO-based human therapy. Here, we directly compare the activities of seven chemically dist...
Source: RNA - February 27, 2024 Category: Genetics & Stem Cells Authors: Chandradhish Ghosh Linda Popella V Dhamodharan Jakob Jung Julia Dietzsch Lars Barquist Claudia H öbartner J örg Vogel Source Type: research
High-resolution RNA tertiary structures in Zika virus stem-loop A for the development of inhibitory small molecules
RNA. 2024 Feb 21:rna.079796.123. doi: 10.1261/rna.079796.123. Online ahead of print.ABSTRACTFlaviviruses such as Zika (ZIKV) and dengue virus (DENV) are positive-sense RNA viruses belonging to Flaviviridae. The flavivirus genome contains a 5' end stem-loop promoter sequence known as stem-loop A (SLA) that is recognized by the flavivirus polymerase NS5 during viral RNA synthesis and 5' guanosine cap methylation. The crystal structures of ZIKV and DENV SLAs show a well-defined fold, consisting of a bottom stem, side loop, and top stem-loop, providing unique interaction sites for small-molecule inhibitors to disrupt the promo...
Source: RNA - February 21, 2024 Category: Genetics & Stem Cells Authors: Jerricho Tipo Keerthi Gottipati Kyung H Choi Source Type: research
High-resolution RNA tertiary structures in Zika virus stem-loop A for the development of inhibitory small molecules
RNA. 2024 Feb 21:rna.079796.123. doi: 10.1261/rna.079796.123. Online ahead of print.ABSTRACTFlaviviruses such as Zika (ZIKV) and dengue virus (DENV) are positive-sense RNA viruses belonging to Flaviviridae. The flavivirus genome contains a 5' end stem-loop promoter sequence known as stem-loop A (SLA) that is recognized by the flavivirus polymerase NS5 during viral RNA synthesis and 5' guanosine cap methylation. The crystal structures of ZIKV and DENV SLAs show a well-defined fold, consisting of a bottom stem, side loop, and top stem-loop, providing unique interaction sites for small-molecule inhibitors to disrupt the promo...
Source: RNA - February 21, 2024 Category: Genetics & Stem Cells Authors: Jerricho Tipo Keerthi Gottipati Kyung H Choi Source Type: research
High-resolution RNA tertiary structures in Zika virus stem-loop A for the development of inhibitory small molecules
RNA. 2024 Feb 21:rna.079796.123. doi: 10.1261/rna.079796.123. Online ahead of print.ABSTRACTFlaviviruses such as Zika (ZIKV) and dengue virus (DENV) are positive-sense RNA viruses belonging to Flaviviridae. The flavivirus genome contains a 5' end stem-loop promoter sequence known as stem-loop A (SLA) that is recognized by the flavivirus polymerase NS5 during viral RNA synthesis and 5' guanosine cap methylation. The crystal structures of ZIKV and DENV SLAs show a well-defined fold, consisting of a bottom stem, side loop, and top stem-loop, providing unique interaction sites for small-molecule inhibitors to disrupt the promo...
Source: RNA - February 21, 2024 Category: Genetics & Stem Cells Authors: Jerricho Tipo Keerthi Gottipati Kyung H Choi Source Type: research
High-resolution RNA tertiary structures in Zika virus stem-loop A for the development of inhibitory small molecules
RNA. 2024 Feb 21:rna.079796.123. doi: 10.1261/rna.079796.123. Online ahead of print.ABSTRACTFlaviviruses such as Zika (ZIKV) and dengue virus (DENV) are positive-sense RNA viruses belonging to Flaviviridae. The flavivirus genome contains a 5' end stem-loop promoter sequence known as stem-loop A (SLA) that is recognized by the flavivirus polymerase NS5 during viral RNA synthesis and 5' guanosine cap methylation. The crystal structures of ZIKV and DENV SLAs show a well-defined fold, consisting of a bottom stem, side loop, and top stem-loop, providing unique interaction sites for small-molecule inhibitors to disrupt the promo...
Source: RNA - February 21, 2024 Category: Genetics & Stem Cells Authors: Jerricho Tipo Keerthi Gottipati Kyung H Choi Source Type: research
High-resolution RNA tertiary structures in Zika virus stem-loop A for the development of inhibitory small molecules
RNA. 2024 Feb 21:rna.079796.123. doi: 10.1261/rna.079796.123. Online ahead of print.ABSTRACTFlaviviruses such as Zika (ZIKV) and dengue virus (DENV) are positive-sense RNA viruses belonging to Flaviviridae. The flavivirus genome contains a 5' end stem-loop promoter sequence known as stem-loop A (SLA) that is recognized by the flavivirus polymerase NS5 during viral RNA synthesis and 5' guanosine cap methylation. The crystal structures of ZIKV and DENV SLAs show a well-defined fold, consisting of a bottom stem, side loop, and top stem-loop, providing unique interaction sites for small-molecule inhibitors to disrupt the promo...
Source: RNA - February 21, 2024 Category: Genetics & Stem Cells Authors: Jerricho Tipo Keerthi Gottipati Kyung H Choi Source Type: research
The molecular language of RNA 5' ends: guardians of RNA identity and immunity
RNA. 2024 Feb 7:rna.079942.124. doi: 10.1261/rna.079942.124. Online ahead of print.ABSTRACTRNA caps are deposited at the 5'end of RNA-polymerase II transcripts. This modification regulates several steps of gene expression, in addition to marking transcripts as self to enable the innate immune system to distinguish them from uncapped foreign RNAs, including those derived from viruses. Specialized immune sensors, such as RIG-I and IFITs, trigger antiviral responses upon recognition of uncapped cytoplasmic transcripts. Interestingly, uncapped transcripts can also be produced by mammalian hosts. For instance, 5'-triphosphate R...
Source: RNA - February 7, 2024 Category: Genetics & Stem Cells Authors: Rodolfo Gamaliel Avila-Bonilla Sara Macias Source Type: research
The molecular language of RNA 5' ends: guardians of RNA identity and immunity
RNA. 2024 Feb 7:rna.079942.124. doi: 10.1261/rna.079942.124. Online ahead of print.ABSTRACTRNA caps are deposited at the 5'end of RNA-polymerase II transcripts. This modification regulates several steps of gene expression, in addition to marking transcripts as self to enable the innate immune system to distinguish them from uncapped foreign RNAs, including those derived from viruses. Specialized immune sensors, such as RIG-I and IFITs, trigger antiviral responses upon recognition of uncapped cytoplasmic transcripts. Interestingly, uncapped transcripts can also be produced by mammalian hosts. For instance, 5'-triphosphate R...
Source: RNA - February 7, 2024 Category: Genetics & Stem Cells Authors: Rodolfo Gamaliel Avila-Bonilla Sara Macias Source Type: research
The molecular language of RNA 5' ends: guardians of RNA identity and immunity
RNA. 2024 Feb 7:rna.079942.124. doi: 10.1261/rna.079942.124. Online ahead of print.ABSTRACTRNA caps are deposited at the 5'end of RNA-polymerase II transcripts. This modification regulates several steps of gene expression, in addition to marking transcripts as self to enable the innate immune system to distinguish them from uncapped foreign RNAs, including those derived from viruses. Specialized immune sensors, such as RIG-I and IFITs, trigger antiviral responses upon recognition of uncapped cytoplasmic transcripts. Interestingly, uncapped transcripts can also be produced by mammalian hosts. For instance, 5'-triphosphate R...
Source: RNA - February 7, 2024 Category: Genetics & Stem Cells Authors: Rodolfo Gamaliel Avila-Bonilla Sara Macias Source Type: research
The molecular language of RNA 5' ends: guardians of RNA identity and immunity
RNA. 2024 Feb 7:rna.079942.124. doi: 10.1261/rna.079942.124. Online ahead of print.ABSTRACTRNA caps are deposited at the 5'end of RNA-polymerase II transcripts. This modification regulates several steps of gene expression, in addition to marking transcripts as self to enable the innate immune system to distinguish them from uncapped foreign RNAs, including those derived from viruses. Specialized immune sensors, such as RIG-I and IFITs, trigger antiviral responses upon recognition of uncapped cytoplasmic transcripts. Interestingly, uncapped transcripts can also be produced by mammalian hosts. For instance, 5'-triphosphate R...
Source: RNA - February 7, 2024 Category: Genetics & Stem Cells Authors: Rodolfo Gamaliel Avila-Bonilla Sara Macias Source Type: research
The molecular language of RNA 5' ends: guardians of RNA identity and immunity
RNA. 2024 Feb 7:rna.079942.124. doi: 10.1261/rna.079942.124. Online ahead of print.ABSTRACTRNA caps are deposited at the 5'end of RNA-polymerase II transcripts. This modification regulates several steps of gene expression, in addition to marking transcripts as self to enable the innate immune system to distinguish them from uncapped foreign RNAs, including those derived from viruses. Specialized immune sensors, such as RIG-I and IFITs, trigger antiviral responses upon recognition of uncapped cytoplasmic transcripts. Interestingly, uncapped transcripts can also be produced by mammalian hosts. For instance, 5'-triphosphate R...
Source: RNA - February 7, 2024 Category: Genetics & Stem Cells Authors: Rodolfo Gamaliel Avila-Bonilla Sara Macias Source Type: research
The molecular language of RNA 5' ends: guardians of RNA identity and immunity
RNA. 2024 Feb 7:rna.079942.124. doi: 10.1261/rna.079942.124. Online ahead of print.ABSTRACTRNA caps are deposited at the 5'end of RNA-polymerase II transcripts. This modification regulates several steps of gene expression, in addition to marking transcripts as self to enable the innate immune system to distinguish them from uncapped foreign RNAs, including those derived from viruses. Specialized immune sensors, such as RIG-I and IFITs, trigger antiviral responses upon recognition of uncapped cytoplasmic transcripts. Interestingly, uncapped transcripts can also be produced by mammalian hosts. For instance, 5'-triphosphate R...
Source: RNA - February 7, 2024 Category: Genetics & Stem Cells Authors: Rodolfo Gamaliel Avila-Bonilla Sara Macias Source Type: research
Fungi of the order Mucorales express a "sealing-only" tRNA ligase
RNA. 2024 Feb 2:rna.079957.124. doi: 10.1261/rna.079957.124. Online ahead of print.ABSTRACTSome eukaryotic pre-tRNAs contain an intron that is removed by a dedicated set of enzymes. Intron-containing pre-tRNAs are cleaved by tRNA splicing endonuclease (TSEN), followed by ligation of the two exons and release of the intron. Fungi use a "heal and seal" pathway that requires three distinct catalytic domains of the tRNA ligase enzyme, Trl1. In contrast, humans use a "direct ligation" pathway carried out by RTCB, an enzyme completely unrelated to Trl1. Because of these mechanistic differences, Trl1 has been proposed as a promis...
Source: RNA - February 2, 2024 Category: Genetics & Stem Cells Authors: Khondakar Sayef Ahammed Ambro van Hoof Source Type: research
