Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Silencing by the miRNA-guided RNA induced silencing complex (miRISC) is dependent on Ago2-chaperoned base pairing between the miRNA 5' seed (5'S) and a complementary sequence in the 3' untranslated region of an mRNA. Prevailing mechanistic understanding posits that initial 5'S pairing can further allow functional base pair expansion into the 3' non-seed (3'NS), while functionally distinct non-canonical pairing was reported between only the 3'NS and the mRNA coding sequence. We developed single-molecule kinetics through equilibrium Poisson sampling (SiMKEPS) to measure highly precise binding and dissociation rate constants of varying-length target sequences to 5'S and 3'NS in a paradigmatic miRISC isolated from human cells, revealing distinct stable states of miRISC with mutually exclusive 5'S and 3'NS pairing. Our data suggest conformational rearrangements of the Ago2-bound miRNA that regulate alternative 5'S- and 3'NS-driven target recognition. The resulting model reconciles previously disparate observations and deepens our acumen for successfully marshaling RNA silencing therapies.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045379 | PMC |
| http://dx.doi.org/10.21203/rs.3.rs-6422368/v1 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A unifying model for microRNA-guided silencing of messenger RNAs.
Res Sq
April 2025
Single Molecule Analysis Group and Center for RNA Biomedicine, Department of Chemistry, University of Michigan, Ann Arbor, Michigan, 48109, United States.
Silencing by the miRNA-guided RNA induced silencing complex (miRISC) is dependent on Ago2-chaperoned base pairing between the miRNA 5' seed (5'S) and a complementary sequence in the 3' untranslated region of an mRNA. Prevailing mechanistic understanding posits that initial 5'S pairing can further allow functional base pair expansion into the 3' non-seed (3'NS), while functionally distinct non-canonical pairing was reported between only the 3'NS and the mRNA coding sequence. We developed single-molecule kinetics through equilibrium Poisson sampling (SiMKEPS) to measure highly precise binding and dissociation rate constants of varying-length target sequences to 5'S and 3'NS in a paradigmatic miRISC isolated from human cells, revealing distinct stable states of miRISC with mutually exclusive 5'S and 3'NS pairing.
View Article and Find Full Text PDFA unifying model for microRNA-guided silencing of messenger RNAs.
bioRxiv
March 2025
Single Molecule Analysis Group and Center for RNA Biomedicine, Department of Chemistry, University of Michigan, Ann Arbor, Michigan, 48109, United States.
Silencing by the miRNA-guided RNA induced silencing complex (miRISC) is dependent on Ago2-chaperoned base pairing between the miRNA 5' seed (5'S) and a complementary sequence in the 3' untranslated region of an mRNA. Prevailing mechanistic understanding posits that initial 5'S pairing can further allow functional base pair expansion into the 3' non-seed (3'NS), while functionally distinct non-canonical pairing was reported between only the 3'NS and the mRNA coding sequence. We developed single-molecule kinetics through equilibrium Poisson sampling (SiMKEPS) to measure highly precise binding and dissociation rate constants of varying-length target sequences to 5'S and 3'NS in a paradigmatic miRISC isolated from human cells, revealing distinct stable states of miRISC with mutually exclusive 5'S and 3'NS pairing.
View Article and Find Full Text PDFC isotope enrichment of the central trityl carbon decreases fluid solution electron spin relaxation times.
J Magn Reson
September 2020
Department of Chemistry and Biochemistry, University of Denver, Denver, CO 80210, USA. Electronic address:
Electron spin relaxation times for perdeuterated Finland trityl 99% enriched in C at the central carbon (C-dFT) were measured in phosphate buffered saline (pH = 7.2) (PBS) solution at X-band. The anisotropic C hyperfine (A = A = 18 ± 2, A = 162 ± 1 MHz) and g values (2.
View Article and Find Full Text PDFBDS Precise Point Positioning for Seismic Displacements Monitoring: Benefit from the High-Rate Satellite Clock Corrections.
Sensors (Basel)
December 2016
GNSS Research Center, Wuhan University, 129 Luoyu Road, Wuhan 430079, China.
In order to satisfy the requirement of high-rate high-precision applications, 1 Hz BeiDou Navigation Satellite System (BDS) satellite clock corrections are generated based on precise orbit products, and the quality of the generated clock products is assessed by comparing with those from the other analysis centers. The comparisons show that the root mean square (RMS) of clock errors of geostationary Earth orbits (GEO) is about 0.63 ns, whereas those of inclined geosynchronous orbits (IGSO) and medium Earth orbits (MEO) are about 0.
View Article and Find Full Text PDF[Rovibrational state distributions of H2 in collisional energy transfer between NaK (6(1)sigma(+)) and H2].
Guang Pu Xue Yu Guang Pu Fen Xi
December 2012
School of Sciences, Xi'an Jiaotong University, Xi'an 710049, China.
The electronic to rovibrational energy transfer between the high-lying 6(1)sigma(+) state of NaK and H2 was investigated. The 6(1)sigma(+) state was excited using the optical-optical double resonance technique. Radiative processes were monitored by fluorescence from the 6(1)sigma(+) state to the ground 1(1)sigma(+) state.
View Article and Find Full Text PDF