Comparative Analysis of the Higher-Order Structure of RNA

Gutell, Robin R.

doi:10.1007/978-1-4614-4954-6_2

Cited by 7 publications

(5 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistently, RNAstructure ( 36 , 37 ) predicts that the base-pairing profile with +5G-C4 usually confers a lesser stability than the noncanonical register. The thermodynamic instability of this base pair might be due to the lack of hydrogen bonding in the flanking mispairs being unable to overcome the electrostatic repulsion of the phosphates on the 5′ss and U1 strands ( 38 ).…”

Section: Resultsmentioning

confidence: 99%

Noncanonical registers and base pairs in human 5′ splice-site selection

Tan

Zhong

et al. 2016

Nucleic Acids Res

View full text Add to dashboard Cite

Accurate recognition of splice sites is essential for pre-messenger RNA splicing. Mammalian 5′ splice sites are mainly recognized by canonical base-pairing to the 5′ end of U1 small nuclear RNA, yet we described multiple noncanonical base-pairing registers by shifting base-pair positions or allowing one-nucleotide bulges. By systematic mutational and suppressor U1 analyses, we prove three registers involving asymmetric loops and show that two-nucleotide bulges but not longer can form in this context. Importantly, we established that a noncanonical uridine-pseudouridine interaction in the 5′ splice site/U1 helix contributes to the recognition of certain 5′ splice sites. Thermal melting experiments support the formation of noncanonical registers and uridine-pseudouridine interactions. Overall, we experimentally validated or discarded the majority of predicted noncanonical registers, to derive a list of 5′ splice sites using such alternative mechanisms that is much different from the original. This study allows not only the mechanistic understanding of the recognition of a wide diversity of mammalian 5′ splice sites, but also the future development of better splice-site scoring methods that reliably predict the effects of disease-causing mutations at these sequences.

show abstract

Section: Resultsmentioning

confidence: 99%

Noncanonical registers and base pairs in human 5′ splice-site selection

Tan

Zhong

et al. 2016

Nucleic Acids Res

View full text Add to dashboard Cite

show abstract

“…R-proteins are colored as follows: S4 (purple); S16 (blue); S17 (green); and S20 (yellow). (b) Binding sites of the r-proteins overlaid onto the 5′ domain rRNA secondary structure diagram adapted from the Comparative RNA Web site (CRW) . Contacts between the r-proteins and rRNA are defined to be within a 5 Å cutoff based on the crystal structure.…”

Section: Methodsmentioning

confidence: 99%

Structural Intermediates and Folding Events in the Early Assembly of the Ribosomal Small Subunit

2013

View full text Add to dashboard Cite

Using all-atom explicit solvent molecular dynamics (MD) simulations, we investigated the early structural intermediates of the 5' domain of the 16S rRNA in Escherichia coli upon the removal of the primary binding r-proteins S4, S17, and S20 and the secondary binding r-protein S16. Removal of each r-protein corresponded to the disappearance of subdomains with correlated dynamics. Correlation-based network analysis of the MD trajectories of the naked rRNA showed that the different subdomains are connected via multiple pathways with high betweenness. These pathways cross at the internal loop of helix 17 (h17) in the five-way junction (5WJ). The structure of the internal loop is disrupted by the binding of S17 and rescued by the addition of S16, suggesting an important function of the secondary binding protein in biasing the rRNA folding landscape toward the native basin. Using structure-based Gō simulations, we investigated the folding barriers of the lower four-way junction (4WJ) with h6, which is the primary binding site of S20 and the first to be transcribed. The folding of the 4WJ is consistent with the protection patterns observed in hydroxyl radical footprinting. Results from the all-atom simulations show that the fluctuations in the 5WJ are independent of the fluctuations in the 4WJ, suggesting that the subdomains fold independently and are stabilized by primary r-proteins.

show abstract

“…This mechanical unfolding becomes the rate-limiting step of degradation [94], and because the global topology of the substrate dictates its resistance against such unfolding, the topology of the folded chain influences its degradation rate [29]. Interestingly, transcripts can also fold into higher-order structures [95][96][97], thus making their mechanical unwinding a prerequisite for degradation. However, unraveling such principles awaits the discovery of 3D structures of several mRNAs.…”

Section: Additional Factors That Influence Mrna Half-lifementioning

confidence: 99%

Genome‐scale molecular principles of mRNA half‐life regulation in yeast

et al. 2021

View full text Add to dashboard Cite

Precise control of protein and messenger RNA (mRNA) degradation is essential for cellular metabolism and homeostasis. Controlled and specific degradation of both molecular species necessitates their engagements with the respective degradation machineries; this engagement involves a disordered/unstructured segment of the substrate traversing the degradation tunnel of the machinery and accessing the catalytic sites. However, while molecular factors influencing protein degradation have been extensively explored on a genome scale, and in multiple organisms, such a comprehensive understanding remains missing for mRNAs. Here, we analyzed multiple genome-scale experimental yeast mRNA half-life data in light of experimentally derived mRNA secondary structures and protein binding data, along with high-resolution X-ray crystallographic structures of the RNase machines. Results unraveled a consistent genome-scale trend that mRNAs comprising longer terminal and/or internal unstructured segments have significantly shorter half-lives; the lengths of the 5 0 -terminal, 3 0 -terminal, and internal unstructured segments that affect mRNA half-life are compatible with molecular structures of the 5 0 exo-, 3 0 exo-, and endoribonuclease machineries. Sequestration into ribonucleoprotein complexes elongates mRNA half-life, presumably by burying ribonuclease engagement sites under oligomeric interfaces. After gene duplication, differences in terminal unstructured lengths, proportions of internal unstructured segments, and oligomerization modes result in significantly altered half-lives of paralogous mRNAs. Side-by-side comparison of molecular principles underlying controlled protein and mRNA degradation in yeast unravels their remarkable mechanistic similarities and suggests how the intrinsic structural features of the two molecular species, at two different levels of the central dogma, regulate their half-lives on genome scale.

show abstract

Comparative Analysis of the Higher-Order Structure of RNA

Cited by 7 publications

References 58 publications

Noncanonical registers and base pairs in human 5′ splice-site selection

Noncanonical registers and base pairs in human 5′ splice-site selection

Structural Intermediates and Folding Events in the Early Assembly of the Ribosomal Small Subunit

Genome‐scale molecular principles of mRNA half‐life regulation in yeast

Contact Info

Product

Resources

About