scholarly journals PHDcleav: a SVM based method for predicting human Dicer cleavage sites using sequence and secondary structure of miRNA precursors

2013 ◽  
Vol 14 (S14) ◽  
Author(s):  
Firoz Ahmed ◽  
Rakesh Kaundal ◽  
Gajendra PS Raghava
2017 ◽  
Author(s):  
Igor I. Titov ◽  
Pavel S. Vorozheykin

AbstractBackgroundMicroRNAs proceeds through the different canonical and non-canonical pathways; the most frequent of the non-canonical ones is the splicing-dependent biogenesis of mirtrons. We compare the mirtrons and non-mirtrons of human and mouse to explore how their maturation appears in the precursor structure around the miRNA.ResultsWe found the coherence of the overhang lengths what indicates the dependence between the cleavage sites. To explain this dependence we suggest the 2-lever model of the Dicer structure that couples the imprecisions in Drosha and Dicer. Considering the secondary structure of all animal pre-miRNAs we confirmed that single-stranded nucleotides tend to be located near the miRNA boundaries and in its center and are characterized by a higher mutation rate. The 5′ end of the canonical 5′ miRNA approaches the nearest single-stranded nucleotides what suggests the extension of the loop-counting rule from the Dicer to the Drosha cleavage site. A typical structure of the annotated mirtron pre-miRNAs differs from the canonical pre-miRNA structure and possesses the 1- and 2nt hanging ends at the hairpin base. Together with the excessive variability of the mirtron Dicer cleavage site (that could be partially explained by guanine at its ends inherited from splicing) this is one more evidence for the 2-lever model. In contrast with the canonical miRNAs the mirtrons have higher snp densities and their pre-miRNAs are inversely associated with diseases. Therefore we supported the view that mirtrons are under positive selection while canonical miRNAs are under negative one and we suggested that mirtrons are an intrinsic source of silencing variability which produces the disease-promoting variants. Finally, we considered the interference of the pre-miRNA structure and the U2snRNA:pre-mRNA basepairing. We analyzed the location of the branchpoints and found that mirtron structure tends to expose the branchpoint site what suggests that the mirtrons can readily evolve from occasional hairpins in the immediate neighbourhood of the 3′ splice site.ConclusionThe miRNA biogenesis manifests itself in the footprints of the secondary structure. Close inspection of these structural properties can help to uncover new pathways of miRNA biogenesis and to refine the known miRNA data, in particular, new non-canonical miRNAs may be predicted or the known miRNAs can be re-classified.


2016 ◽  
Vol 473 (21) ◽  
pp. 3755-3758 ◽  
Author(s):  
Ján A. Miernyk

The human mitochondrial glutamate dehydrogenase isoenzymes (hGDH1 and hGDH2) are abundant matrix-localized proteins encoded by nuclear genes. The proteins are synthesized in the cytoplasm, with an atypically long N-terminal mitochondrial targeting sequence (MTS). The results of secondary structure predictions suggest the presence of two α-helices within the N-terminal region of the MTS. Results from deletion analyses indicate that individual helices have limited ability to direct protein import and matrix localization, but that there is a synergistic interaction when both helices are present [Biochem. J. (2016) 473, 2813–2829]. Mutagenesis of the MTS cleavage sites blocked post-import removal of the presequences, but did not impede import. The authors propose that the high matrix levels of hGDH can be attributed to the unusual length and secondary structure of the MTS.


2015 ◽  
Vol 16 (12) ◽  
pp. 8110-8127 ◽  
Author(s):  
Julia Starega-Roslan ◽  
Tomasz Witkos ◽  
Paulina Galka-Marciniak ◽  
Wlodzimierz Krzyzosiak

1984 ◽  
Vol 220 (1) ◽  
pp. 105-116 ◽  
Author(s):  
K V Hadjiolova ◽  
O I Georgiev ◽  
V V Nosikov ◽  
A A Hadjiolov

The initial endonuclease cleavage site in 32 S pre-rRNA (precursor to rRNA) is located within the rate rDNA sequence by S1-nuclease protection mapping of purified nucleolar 28 S rRNA and 12 S pre-rRNA. The heterogeneous 5′- and 3′-termini of these rRNA abut and map within two CTC motifs in tSi2 (internal transcribed spacer 2) located at 50-65 and 4-20 base-pairs upstream from the homogeneous 5′-end of the 28 S rRNA gene. These results show that multiple endonuclease cleavages occur at CUC sites in tSi2 to generate 28 S rRNA and 12 S pre-rRNA with heterogeneous 5′- and 3′-termini, respectively. These molecules have to be processed further to yield mature 28 S and 5.8 S rRNA. Thermal-denaturation studies revealed that the base-pairing association in the 12 S pre-rRNA:28 S rRNA complex is markedly stronger than that in the 5.8 S:28 S rRNA complex. The sequence of about one-quarter (1322 base-pairs) of the 5′-part of the rat 28 S rDNA was determined. A computer search reveals the possibility that the cleavage sites in the CUC motifs are single-stranded, flanked by strongly base-paired GC tracts, involving tSi2 and 28 S rRNA sequences. The subsequent nuclease cleavages, generating the termini of mature rRNA, seem to be directed by secondary-structure interactions between 5.8 S and 28 S rRNA segments in pre-rRNA. An analysis for base-pairing among evolutionarily conserved sequences in 32 S pre-rRNA suggests that the cleavages yielding mature 5.8 S and 28 S rRNA are directed by base-pairing between (i) the 3′-terminus of 5.8 S rRNA and the 5′-terminus of 28 S rRNA and (ii) the 5′-terminus of 5.8 S rRNA and internal sequences in domain I of 28 S rRNA. A general model for primary- and secondary-structure interactions in pre-rRNA processing is proposed, and its implications for ribosome biogenesis in eukaryotes are briefly discussed.


1989 ◽  
Vol 35 (1) ◽  
pp. 189-194 ◽  
Author(s):  
Prasun K. Datta ◽  
Lynda K. Hawkins ◽  
Ramesh Gupta

The gene for the elongator (internal) methionine transfer RNA [Formula: see text] in the archaebacterium Halobacterium volcanii contains a 75 base pair intron (intervening sequence) and lacks the 3′-terminal CCA sequence of the mature tRNA. There is a single copy of this gene in the genome and it is expressed. Northern hybridization experiments indicate that the precursor is processed to produce mature tRNA and a free intron species. A secondary structure of the transcript can be formed in which the anticodon stem of the tRNA is extended. Two symmetrically placed three-base bulge loops separated by a 4 base pair stem are present in this extension. The cleavage sites for the removal of the intron are placed between the middle and 3′ residues of these loops.Key words: archaebacteria, methionine-tRNA, intron, splicing.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Pengyu Liu ◽  
Jiangning Song ◽  
Chun-Yu Lin ◽  
Tatsuya Akutsu

Abstract Background Human dicer is an enzyme that cleaves pre-miRNAs into miRNAs. Several models have been developed to predict human dicer cleavage sites, including PHDCleav and LBSizeCleav. Given an input sequence, these models can predict whether the sequence contains a cleavage site. However, these models only consider each sequence independently and lack interpretability. Therefore, it is necessary to develop an accurate and explainable predictor, which employs relations between different sequences, to enhance the understanding of the mechanism by which human dicer cleaves pre-miRNA. Results In this study, we develop an accurate and explainable predictor for human dicer cleavage site – ReCGBM. We design relational features and class features as inputs to a lightGBM model. Computational experiments show that ReCGBM achieves the best performance compared to the existing methods. Further, we find that features in close proximity to the center of pre-miRNA are more important and make a significant contribution to the performance improvement of the developed method. Conclusions The results of this study show that ReCGBM is an interpretable and accurate predictor. Besides, the analyses of feature importance show that it might be of particular interest to consider more informative features close to the center of the pre-miRNA in future predictors.


2000 ◽  
Vol 74 (22) ◽  
pp. 10390-10400 ◽  
Author(s):  
Antonio Vera ◽  
José-Antonio Daròs ◽  
Ricardo Flores ◽  
Carmen Hernández

ABSTRACT Carnation small viroid-like RNA (CarSV RNA) and its homologous DNA are the two forms of a unique plant retroviroid-like system. CarSV RNA is a 275-nucleotide noninfectious viroid-like RNA, present in certain carnation plants, which can adopt hammerhead structures in both polarity strands and self-cleave accordingly. CarSV DNA is organized as a series of head-to-tail multimers forming part of extrachromosomal elements in which CarSV DNA sequences are fused to sequences of carnation etched ring virus (CERV), a plant pararetrovirus. Analysis of more than 30 CarSV-CERV DNA junctions showed that distinct regions of the viral genome seem able to interact with CarSV DNA. All these junctions were short nucleotide stretches common to both CarSV and CERV DNAs. This suggests a polymerase-driven mechanism for their origin involving an enzyme with low processivity, most likely the viral reverse transcriptase. This view was further supported by the observation that most of CarSV sequences forming part of the junctions correspond either to strong secondary structure motifs in the conformation proposed for CarSV RNA or to its self-cleavage sites, which may have facilitated polymerase jumping. Accompanying the most-abundant CarSV RNA, a series of CarSV RNAs with sequence deletions were previously characterized. Here we have identified some of their corresponding DNA forms, together with other CarSV DNA forms with deletions not found in any CarSV RNA species identified so far. Some of these CarSV DNA forms have also been detected fused to CERV sequences. The existence of these shortened CarSV DNA versions may provide a continuous input of their corresponding transcripts and explain the persistence of CarSV RNAs with defective hammerhead structures for which an RNA-RNA model of amplification seems unlikely.


Author(s):  
John P. Robinson ◽  
J. David Puett

Much work has been reported on the chemical, physical and morphological properties of urinary Tamm-Horsfall glycoprotein (THG). Although it was once reported that cystic fibrotic (CF) individuals had a defective THG, more recent data indicate that THG and CF-THG are similar if not identical.No studies on the conformational aspects have been reported on this glycoprotein using circular dichroism (CD). We examined the secondary structure of THG and derivatives under various conditions and have correlated these results with quaternary structure using electron microscopy.THG was prepared from normal adult males and CF-THG from a 16-year old CF female by the method of Tamm and Horsfall. CF female by the method of Tamm and Horsfall.


Sign in / Sign up

Export Citation Format

Share Document