Involvement of Helix 34 of 16 S rRNA in Decoding and Translocation on the Ribosome

Kubarenko, Andriy V.; Сергиев, Петр В.; Wintermeyer, Wolfgang; Dontsova, Olga А.; Rodnina, Marina V.

doi:10.1074/jbc.m608060200

Cited by 17 publications

(12 citation statements)

References 50 publications

(41 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, base changes at C972 , G963 and A964 produced moderately deleterious, but dominant growth defects, whereas mutations at G973 strongly impaired cell growth (61). Finally, the physical proximity of the C972:G963 to the A-site ASL explains the observed effects of mutations in the region on the fidelity of A-site decoding (62). In summary, both the 579C > G (m.1226C > G) and the 580G>A (m.1227G>A) mutations are expected to be highly disruptive to the function of the mitoribosome.…”

Section: Resultsmentioning

confidence: 99%

The role of the mitochondrial ribosome in human disease: searching for mutations in 12S mitochondrial rRNA with high disruptive potential

Smith¹,

Elson²,

Greaves³

et al. 2013

Human Molecular Genetics

View full text Add to dashboard Cite

Mutations of mitochondrial DNA are linked to many human diseases. Despite the identification of a large number of variants in the mitochondrially encoded rRNA (mt-rRNA) genes, the evidence supporting their pathogenicity is, at best, circumstantial. Establishing the pathogenicity of these variations is of major diagnostic importance. Here, we aim to estimate the disruptive effect of mt-rRNA variations on the function of the mitochondrial ribosome. In the absence of direct biochemical methods to study the effect of mt-rRNA variations, we relied on the universal conservation of the rRNA fold to infer their disruptive potential. Our method, named heterologous inferential analysis or HIA, combines conservational information with functional and structural data obtained from heterologous ribosomal sources. Thus, HIA's predictive power is superior to the traditional reliance on simple conservation indexes. By using HIA, we have been able to evaluate the disruptive potential for a subset of uncharacterized 12S mt-rRNA variations. Our analysis revealed the existence of variations in the rRNA component of the human mitoribosome with different degrees of disruptive power. In cases where sufficient information regarding the genetic and pathological manifestation of the mitochondrial phenotype is available, HIA data can be used to predict the pathogenicity of mt-rRNA mutations. In other cases, HIA analysis will allow the prioritization of variants for additional investigation. Eventually, HIA-inspired analysis of potentially pathogenic mt-rRNA variations, in the context of a scoring system specifically designed for these variants, could lead to a powerful diagnostic tool.

show abstract

Section: Resultsmentioning

confidence: 99%

The role of the mitochondrial ribosome in human disease: searching for mutations in 12S mitochondrial rRNA with high disruptive potential

Smith¹,

Elson²,

Greaves³

et al. 2013

Human Molecular Genetics

View full text Add to dashboard Cite

show abstract

“…Transition (ts)/transversion (tv) ratio of the cereal mt genes also was only two-fifths of that of the ct genes, of which range was between 0.7 and 0.9 for the former and Reference RNA-RNA cross-linking h3, h4, h5, h6, h7a, h7 Pardon and Wagner (1995) Intersubunit bridge h14, h20, h23, h24, h25, h27, h44a, h45 Belanger et al (2002Belanger et al ( , 2004Belanger et al ( , 2005, Ghosh and Joseph (2005), Kubarenko et al (2006) Intersubunit assembly h1, h5, h15, h24, h27, h31, h34 Thanarai et al (1988), Belanger et al (2002Belanger et al ( , 2004Belanger et al ( , 2005, Yassin et al (2005), Kubarenko et al (2006) 30S subunit assembly h39, h40, h41 Ghosh and Joseph (2005) A site h18, h31, h34, h44a Yassin et al (2005) P site h31, h44a, h45 Yassin et al (2005) Translation accuracy h1, h2, h18, h24, h27, h31, h34, h35 Peptide elongation h18, h34, h43 Powers and Noller (1990), Dragon et al (1996), Lafontaine and Tollervey (2001) Peptide chain termination h23a, h34, h44a Murgola et al (1988Murgola et al ( , 1995, Prescott and Goringer (1990), Hanfler et al (1990), Goringer et al (1991), Prescott et al (1991), Gregory and Dahlberg (1995) 1) Helix numbers are cited from Ghosh and Joseph (2005), which correspond to helix numbers encircled by red line in Fig. 2.…”

Section: Features Of Base Substitutions Occurred In the Organellar Gementioning

confidence: 99%

Evolutionary dynamics of wheat mitochondrial gene structure with special remarks on the origin and effects of RNA editing in cereals

et al. 2008

View full text Add to dashboard Cite

We investigated the evolutionary dynamics of wheat mitochondrial genes with respect to their structural differentiation during organellar evolution, and to mutations that occurred during cereal evolution. First, we compared the nucleotide sequences of three wheat mitochondrial genes to those of wheat chloroplast, α-proteobacterium and cyanobacterium orthologs. As a result, we were able to (1) differentiate the conserved and variable segments of the orthologs, (2) reveal the functional importance of the conserved segments, and (3) provide a corroborative support for the α-proteobacterial and cyanobacterial origins of those mitochondrial and chloroplast genes, respectively. Second, we compared the nucleotide sequences of wheat mitochondrial genes to those of rice and maize to determine the types and frequencies of base changes and indels occurred in cereal evolution. Our analyses showed that both the evolutionary speed, in terms of number of base substitutions per site, and the transition/transversion ratio of the cereal mitochondrial genes were less than two-fifths of those of the chloroplast genes. Eight mitochondrial gene groups differed in their evolutionary variability, RNA and Complex I (nad) genes being most stable whereas Complex V (atp) and ribosomal protein genes most variable. C-to-T transition was the most frequent type of base change; C-to-G and G-to-C transversions occurred at lower rates than all other changes. The excess of C-to-T transitions was attributed to C-to-U RNA editing that developed in early stage of vascular plant evolution. On the contrary, the editing of C residues at cereal T-to-C transition sites developed mostly during cereal divergence. Most indels were associated with short direct repeats, suggesting intra-and intermolecular recombination as an important mechanism for their origin. Most of the repeats associated with indels were di-or trinucleotides, although no preference was noticed for their sequences. The maize mt genome was characterized by a high incidence of indels, comparing to the wheat and rice mt genomes.

show abstract

“…Specific nucleotides in these helices that contact A-, P-, or E-site tRNAs and mRNA have also been identified in crystallography studies (e.g., Ogle et al 2001;Yusupov et al 2001;Selmer et al 2006). Nucleotides involved in decoding have been revealed by mutational analysis, in which translation efficiency, fidelity, or tRNA translocation have been affected, as well as resistance to error-causing antibiotics (De Stasio et al 1989;Recht et al 1999;Kubarenko et al 2006;Garcia-Ortega et al 2008;Saraiya et al 2008). These findings established the importance of the proper sequence and structure of the decoding center in controlling tRNA selection and translocation, and ensuring efficient, accurate translation (Ogle et al 2003;Ogle and Ramakrishnan 2005;Frank et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Loss of rRNA modifications in the decoding center of the ribosome impairs translation and strongly delays pre-rRNA processing

Liang

Liu²,

Fournier³

2009

RNA

195

181

View full text Add to dashboard Cite

The ribosome decoding center is rich in modified rRNA nucleotides and little is known about their effects. Here, we examine the consequences of systematically deleting eight pseudouridine and 29-O-methylation modifications in the yeast decoding center. Loss of most modifications individually has no apparent effect on cell growth. However, deletions of 2-3 modifications in the A-and P-site regions can cause (1) reduced growth rates (;15%-50% slower); (2) reduced amino acid incorporation rates (14%-24% slower); and (3) a significant deficiency in free small subunits. Negative and positive interference effects were observed, as well as strong positional influences. Notably, blocking formation of a hypermodified pseudouridine in the P region delays the onset of the final cleavage event in 18S rRNA formation (;60% slower), suggesting that modification at this site could have an important role in modulating ribosome synthesis.

show abstract

Involvement of Helix 34 of 16 S rRNA in Decoding and Translocation on the Ribosome

Cited by 17 publications

References 50 publications

The role of the mitochondrial ribosome in human disease: searching for mutations in 12S mitochondrial rRNA with high disruptive potential

The role of the mitochondrial ribosome in human disease: searching for mutations in 12S mitochondrial rRNA with high disruptive potential

Evolutionary dynamics of wheat mitochondrial gene structure with special remarks on the origin and effects of RNA editing in cereals

Loss of rRNA modifications in the decoding center of the ribosome impairs translation and strongly delays pre-rRNA processing

Contact Info

Product

Resources

About