Global importance of RNA secondary structures in protein-coding sequences

Abstract

We show that the nucleotide distribution within codons is biased in all taxa of life on a global scale. Thereby, RNA secondary structures that require base-pairing between the position 1 of a codon with the position 1 of an opposing codon (here named RNA secondary structure class c1) are under-represented. We conclude that this bias may result from the co-evolution of codon sequence and mRNA secondary structure, suggesting that RNA secondary structures are generally important in protein coding regions of mRNAs. The above result also implies that codon position 2 has a smaller influence on the amino acid choice than codon position 1.

Ribosome Pausing at Inefficient Codons at the End of the Replicase Coding Region Is Important for Hepatitis C Virus Genome Replication

“…In the transcriptome reads, low level of minus-strand reads compared to plus-strand reads are detected ( Figure 2C), which is consistent with the ratio of plus to minus strand abundancies of about 5:1 to 15:1 in HCV replicating cells [22,58]. The frequencies of RNA secondary structure classes in which opposing codons would be required to pair (as shown in the inserts) were calculated for conserved HCV sequences [60]. For example, in class c1, position 1 of one codon would be required to pair with position 1 of an opposing codon, whereas in class c2, position 2 of one codon would be required to pair with position 2 of an opposing codon [60].…”

“…Windows of 200 nucleotides (nts) were moved in steps of 5 nts, and for each nucleotide, the means of class frequencies are calculated from all windows containing this given nt. As a result, the plots show if a certain RNA secondary structure class is under-represented due to selection pressure, which would suggest the presence of a functional RNA secondary structure [60]. Thereby, under-representation of RNA secondary structure class c1 indicates the general importance of codon position 1 to determine a specific amino acid, whereas under-representation of class c2 indicates the importance of codon position 2, which often determines hydrophobic amino acids in membrane standing protein regions [60].…”

Hepatitis C Virus Translation Regulation

“…indicating weakly similar AA properties. The dot indicating similarity between AAs at position 7 in terms of being charged but neglecting charge reversal have been removed, since charge reversal can have serious consequences for proteins [231]. Figure 1.…”

Widespread selection for high and low secondary structure in coding sequences across all domains of life

“…underrepresented, suggesting presence of selective forces (Fricke et al 2018). Noteworthily, Hoede et al (2006) have proposed that selection also acts on the level of DNA structure during transcription and favors local intra-strand secondary structures to reduce the extent of transcriptional mutagenesis, a phenomenon that can particularly observed at highly expressed genes.…”

“…However, silent substitutions will necessarily result in altered codon composition of a gene and further have the potential to alter a gene's GC-content, both being features that can indeed be subject to selection (Sharp et al 1995). Moreover, silent substitutions can change the secondary structure of an mRNA, thereby affecting the process of translation (Babendure et al 2006, Kudla et al 2009, Mao et al 2014, Huang et al 2019) and non-random patterns of secondary structures within protein coding genes in different species have been explained by natural selection (Katz and Burge 2003, Chamary and Hurst 2005, Hoede et al 2006, Fricke et al 2018). However, the currently available data does not allow to assess whether selection that acts on secondary structures within coding sequences represents a peculiarity of a few genomic loci in a limited number of species, or rather a widespread phenomenon, affecting many genes in species throughout the domains of life.…”