AUG_hairpin: prediction of a downstream secondary structure influencing the recognition of a translation start site

Кочетов, А. В.; Palyanov, Andrey; Titov, I. I.; Grigorovich, D. A.; Sarai, Akinori; Колчанов, Н. А.

doi:10.1186/1471-2105-8-318

Cited by 51 publications

(48 citation statements)

References 32 publications

(45 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, a stable secondary structure located 13-17 nucleotides downstream of the start codon could delay 40S movement in the proper position and facilitate the recognition of TIS in a weak context, but the frequency of this signal in eukaryotic transcriptome was not analyzed. (8,9) The results of some computational evaluations showed the potential importance of a nucleotide in position þ5 and a second codon of the CDS as well as some other mRNA regions. (10)(11)(12)(13) The initiation of translation may also sometimes occur at non-AUG codons.…”

Section: Eukaryotic Mrnas and Translation Initiation Mechanismsmentioning

confidence: 99%

“…perfect context, specifically positioned downstream secondary structure, reiterated initiator codon. (1,9,17) Actually, available data on relative translation efficiencies of different context variants as well as the role of other mRNA characteristics are rather limited, and this problem certainly demands further intensive investigation. Currently we may define AUG context as optimal (allowing low-level leaky scanning if any) or suboptimal (potentially allowing noticeable leaky scanning, the efficiency of which depends on the nucleotide combination and may not be predicted accurately).…”

Section: Eukaryotic Mrnas and Translation Initiation Mechanismsmentioning

confidence: 99%

See 1 more Smart Citation

Alternative translation start sites and hidden coding potential of eukaryotic mRNAs

2008

View full text Add to dashboard Cite

SummaryIt is widely suggested that a eukaryotic mRNA typically contains one translation start site and encodes a single functional protein product. However, according to current points of view on translation initiation mechanisms, eukaryotic ribosomes can recognize several alternative translation start sites and the number of experimentally verified examples of alternative translation is growing rapidly. Also, the frequent occurrence of alternative translation events and their functional significance are supported by the results of computational evaluations. The functional role of alternative translation and its contribution to eukaryotic proteome complexity are discussed.

show abstract

Section: Eukaryotic Mrnas and Translation Initiation Mechanismsmentioning

confidence: 99%

Section: Eukaryotic Mrnas and Translation Initiation Mechanismsmentioning

confidence: 99%

Alternative translation start sites and hidden coding potential of eukaryotic mRNAs

2008

View full text Add to dashboard Cite

show abstract

“…1). The mechanism of RAN translation likely involves inefficient RNA splicing and stalling of the ribosome as it scans the hexanucleotide repeat, leading to inappropriate translation without a start codon [134,135]. The G 4 C 2 repeat is translated in all reading frames in both the sense and antisense strands, resulting in several different dipeptides that accumulate specifically within the cells of patients carrying pathogenic (>22) repeat lengths.…”

Section: Alternative Rna-based Mechanismsmentioning

confidence: 99%

Linking RNA Dysfunction and Neurodegeneration in Amyotrophic Lateral Sclerosis

Barmada

2015

Neurotherapeutics

View full text Add to dashboard Cite

The degeneration of motor neurons in amyotrophic lateral sclerosis (ALS) inevitably causes paralysis and death within a matter of years. Mounting genetic and functional evidence suggest that abnormalities in RNA processing and metabolism underlie motor neuron loss in sporadic and familial ALS. Abnormal localization and aggregation of essential RNA-binding proteins are fundamental pathological features of sporadic ALS, and mutations in genes encoding RNA processing enzymes cause familial disease. Also, expansion mutations occurring in the noncoding region of C9orf72-the most common cause of inherited ALS-result in nuclear RNA foci, underscoring the link between abnormal RNA metabolism and neurodegeneration in ALS. This review summarizes the current understanding of RNA dysfunction in ALS, and builds upon this knowledge base to identify converging mechanisms of neurodegeneration in ALS. Potential targets for therapy development are highlighted, with particular emphasis on early and conserved pathways that lead to motor neuron loss in ALS.

show abstract

“…We used the AUG_hairpin program, via which one can evaluate the presence of secondary structure downstream of AUG sites that might influence the recognition of a translation initiation site (38). We assessed whether regions downstream of AUG u1 , AUG u2 , and AUG p form such secondary structures.…”

Section: Secondary Structure Prediction Kozak Sequence Scoring and mentioning

confidence: 99%

“…We checked for differences in secondary structures downstream of each putative start site of SP-A1 that might affect translation initiation. AUG_hairpin is an algorithm that has been developed as a tool to predict such hairpins that may affect translation initiation (38). In ACD= 5=-UTR of SP-A1, all three putative start sites have moderately stable downstream secondary structures that would be able to Fig.…”

Section: Bioinformatic Prediction Of the Translation Initiation Sitementioning

confidence: 99%

Regulation of translation by upstream translation initiation codons of surfactant protein A1 splice variants

Tsotakos

Silveyra

Lin

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Surfactant protein A (SP-A), a molecule with roles in lung innate immunity and surfactant-related functions, is encoded by two genes in humans: SFTPA1 (SP-A1) and SFTPA2 (SP-A2). The mRNAs from these genes differ in their 5′-untranslated regions (5′-UTR) due to differential splicing. The 5′-UTR variant ACD′ is exclusively found in transcripts of SP-A1, but not in those of SP-A2. Its unique exon C contains two upstream AUG codons (uAUGs) that may affect SP-A1 translation efficiency. The first uAUG (u1) is in frame with the primary start codon (p), but the second one (u2) is not. The purpose of this study was to assess the impact of uAUGs on SP-A1 expression. We employed RT-qPCR to determine the presence of exon C-containing SP-A1 transcripts in human RNA samples. We also used in vitro techniques including mutagenesis, reporter assays, and toeprinting analysis, as well as in silico analyses to determine the role of uAUGs. Exon C-containing mRNA is present in most human lung tissue samples and its expression can, under certain conditions, be regulated by factors such as dexamethasone or endotoxin. Mutating uAUGs resulted in increased luciferase activity. The mature protein size was not affected by the uAUGs, as shown by a combination of toeprint and in silico analysis for Kozak sequence, secondary structure, and signal peptide and in vitro translation in the presence of microsomes. In conclusion, alternative splicing may introduce uAUGs in SP-A1 transcripts, which in turn negatively affect SP-A1 translation, possibly affecting SP-A1/SP-A2 ratio, with potential for clinical implication.

show abstract

AUG_hairpin: prediction of a downstream secondary structure influencing the recognition of a translation start site

Cited by 51 publications

References 32 publications

Alternative translation start sites and hidden coding potential of eukaryotic mRNAs

Alternative translation start sites and hidden coding potential of eukaryotic mRNAs

Linking RNA Dysfunction and Neurodegeneration in Amyotrophic Lateral Sclerosis

Regulation of translation by upstream translation initiation codons of surfactant protein A1 splice variants

Contact Info

Product

Resources

About