Biology subjects

Novoa, E. M.

Publications and source records attributed to Novoa, E. M..

3 recordsLinked to original sources

bioRxiv2018

Elucidation of Codon Usage Signatures across the Domains of Life

Due to the degeneracy of the genetic code, multiple codons are translated into the same amino acid. Despite being synonymous, these codons are not equally used. Selective pressures are thought to drive the choice among synonymous codons within a genome, while GC content, which is generally attributed to mutational drift, is the major determinant of interspecies codon usage bias. Here we find that in addition to the bias caused by GC content, inter-species codon usage signatures can also be detected. More specifically, we show that a single amino acid, arginine, is the major contributor to codon usage bias differences across domains of life. We then exploit this finding, and show that the identified domain-specific codon bias signatures can be used to classify a given sequence into its corresponding domain with high accuracy. Considering that species belonging to the same domain share similar tRNA decoding strategies, we then wondered whether the inclusion of codon autocorrelation patterns might improve the classification performance of our algorithm. However, we find that autocorrelation patterns are not domain-specific, and surprisingly, are unrelated to tRNA reusage, in contrast to the common belief. Instead, our results reveal that codon autocorrelation patterns are a consequence of codon optimality throughout a sequence, where highly expressed genes display autocorrelated optimal codons, whereas lowly expressed genes display autocorrelated non-optimal codons.

evolutionary biology↗

bioRxiv2018

mRNA structure dynamics identifies the embryonic RNA regulome

RNA folding plays a crucial role in RNA function. However, our knowledge of the global structure of the transcriptome is limited to steady-state conditions, hindering our understanding of how RNA structure dynamics influences gene function. Here, we have characterized mRNA structure dynamics during zebrafish development. We observe that on a global level, translation guides structure rather than structure guiding translation. We detect a decrease in structure in translated regions, and we identify the ribosome as a major remodeler of RNA structure in vivo. In contrast, we find that 3-UTRs form highly folded structures in vivo, which can affect gene expression by modulating miRNA activity. Furthermore, we find that dynamic 3-UTR structures encode RNA decay elements, including regulatory elements in nanog and cyclin A1, key maternal factors orchestrating the maternal-to-zygotic transition. These results reveal a central role of RNA structure dynamics in gene regulatory programs.

molecular biology↗

bioRxiv2017

Best practices for genome-wide RNA structure analysis: combination of mutational profiles and drop-off information

Genome-wide RNA structure maps have recently become available through the coupling of in vivo chemical probing reagents with next-generation sequencing. Initial analyses relied on the identification of truncated reverse transcription reads to identify the chemically modified nucleotides, but recent studies have shown that mutational signatures can also be used. While these two methods have been employed interchangeably, here we show that they actually provide complementary information. Consequently, analyses using exclusively one of the two methodologies may disregard a significant portion of the structural information. We also show that the identity and sequence environment of the modified nucleotide greatly affect the odds of introducing a mismatch or causing reverse transcriptase drop-off. Finally, we identify specific mismatch signatures generated by dimethyl sulfate probing that can be exploited to remove false positives typically produced in RNA structurome analyses, and how these signatures vary depending on the reverse transcription enzyme used.

bioinformatics↗