bioRxiv Science⌕ Search

bioRxiv · 10.1101/174359

COMPARISONS OF CODING AND NONCODING SEQUENCES TOINFER THE ORIGIN OF CODON USAGE BIAS

Abstract

Codon usage bias is the preferential use of the subset of synonymous codons during translation. In this paper, the comparisons of normalized entropy and GC content between the sequence of coding regions of Escherichia coli k12 and noncoding regions (ncRNA, rRNA) of various organisms were done to shed light on the origin of the codon usage bias.The normalized entropy of the coding regions was found significantly higher than the noncoding regions, suggesting the role of the translation process in shaping codon usage bias. Further, when the position specific GC content of both coding and noncoding regions was analyzed, the GC2 content in coding regions was lower than GC1 and GC2 while in noncoding regions, the GC1, GC2, GC3 contents were approximately equal. This discrepancy is explained by the biased mutation coupled with the presence and absence of selection pressure. The accumulation of CG content occurs in the sequences due to mutation bias in DNA repair and recombination process. In noncoding regions, the mutation is harmful and thus, selected against while due to the degeneracy of codons in coding regions, a mutation in GC3 is neutral and hence, not selected. Thus, the accumulation of GC content occurs in coding regions, and thus codon usage bias occurs.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Mainali, P., Pathak, S.. 2017-08-10. COMPARISONS OF CODING AND NONCODING SEQUENCES TOINFER THE ORIGIN OF CODON USAGE BIAS. https://doi.org/10.1101/174359

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

IER3-N-cadherin axis contributes to apoptosis resistance in dermal fibroblasts under profibrotic conditions

Background: Persistent activation and resistance to apoptosis of dermal fibroblasts contribute to pathological skin fibrosis. Immediate early response 3 (IER3) is a stress-responsive protein involved in cell survival, but its role in cutaneous fibrosis remains unclear. We investigated the functional significance of IER3 in dermal fibroblasts and its potential contribution to fibrosis. Methods: IER3 expression was examined in skin samples from patients with systemic sclerosis, keloids, and hypertrophic scars. Primary human dermal fibroblasts were stimulated with transforming growth factor-{beta}1 (TGF-{beta}1). RNA sequencing, siRNA-mediated gene silencing, quantitative PCR, and flow cytometric apoptosis assays were performed to investigate the downstream mechanisms and functional consequences of IER3 expression. Results: IER3 expression was increased in dermal fibroblasts within fibrotic skin lesions and was induced by TGF-{beta}1 independently of SMAD3 and MEK/ERK signaling. Transcriptomic analysis identified CDH2, encoding N-cadherin, as a downstream target of IER3. Moreover, TGF-{beta}1 induced CDH2 expression in a SMAD3 phosphorylation-dependent manner. IER3 knockdown attenuated TGF-{beta}1-induced CDH2 expression, whereas CDH2 knockdown did not affect IER3 expression. Furthermore, CDH2 knockdown enhanced staurosporine-induced apoptosis in TGF-{beta}1-stimulated fibroblasts, accompanied by a shift in apoptosis-related gene expression toward a pro-apoptotic profile. Conclusion: Our findings identify a previously unrecognized IER3-N-cadherin regulatory axis that may promote dermal fibroblast survival by suppressing apoptosis under profibrotic conditions. Targeting this pathway may represent a novel therapeutic strategy for persistent skin fibrosis.

molecular biology↗

Molecular basis of Cyclin B1-CDK1 recruitment by MAD1

The interaction between Cyclin B1-CDK1 and MAD1 recruits kinase activity to the nuclear pore complex and kinetochore corona to sustain spindle assembly checkpoint (SAC) signaling. Here, we characterize a short linear motif (SLiM) within MAD1 that mediates its interaction with Cyclin B1. This SLiM peptide is specific for B-type cyclins and lacks the canonical "RxL" cyclin-binding consensus sequence, suggesting a distinct mode of cyclin recognition. Using a combination of deep mutational scanning, structural analysis by cryogenic electron microscopy, and binding affinity measurements, we define the molecular basis of the Cyclin B1-MAD1 interaction. These approaches reveal that a short MAD1 peptide binds as an -helix to the RxL-binding hydrophobic patch of Cyclin B1. The interaction employs hydrophobic contacts that overlap with those used by canonical RxL motifs, but is distinguished by additional contacts and sequence features that confer preferential recognition by B-type cyclins while excluding other cyclin types. We also show that the MAD1 motif is sufficient to confer B-type cyclin-specific substrate phosphorylation in mitotic cells. Together, these findings reveal a non-canonical, B-type cyclin-specific helical binding mode that ensures selective Cyclin B1-CDK1 recruitment at two critical stages of SAC signaling, and suggest potential strategies for selective therapeutic targeting of this interaction.

molecular biology↗

Characterizing nascent readthrough transcripts in human cells

Termination of transcription by RNA polymerase II (RNAPII) is critical to appropriately define transcriptome and proteome identity; yet mechanisms of termination regulation are incompletely understood. Current models suggest critical roles for the exonuclease XRN2, which is posited to "torpedo" out RNAPII after degrading uncapped and RNAPII-tethered nascent transcripts and posit an allosteric model wherein elongating RNAPII loses its processivity downstream of the transcription end site (TES) via unknown mechanisms. Here, we used nascent RNA Bru-seq to interrogate transcription termination across 16 human cell lines of distinct lineages, as part of the ENCODE 4 project, to identify key regulatory modes. We find that > 75% of protein-coding genes engage in readthrough transcription under homeostatic conditions. Exposing human cells to oxidative stress or hyperosmotic conditions or splicing inhibitors cause an increase in readthrough transcripts globally. Using an auxin-inducible degradation approach we find that depletion of BRD4, MED14 or XRN2 increases the extent and pervasiveness of readthrough transcripts while depletion of SUPT16H results in shorter readthrough transcripts. Our study provides a comprehensive view of homeostatic readthrough transcripts in human cells and delineates key components regulating transcription termination.

molecular biology↗