SGM Journals

Research explained · RNA virus genomes

What is the extra string of A’s in chikungunya RNA?

Prototype chikungunya strain S27 has a run of A’s near the end of its RNA, before the terminal tail. The run began at the same position in the copies researchers sequenced, but its length varied. The authors proposed that the viral copying enzyme might slip on the repeated sequence. [1]

See original studies View the SGM research record

What the team found in the S27 sequence

Genome length
The authors counted 11,805 nucleotides after excluding the cap nucleotide, internal A tract and terminal A tail.
Keeping the two A runs out of the total gave the team a length separate from the variable sequence. [1]
Two regions that code for proteins
The genome contains two large regions that code for long protein chains, one structural and one nonstructural.
The team compared known cut sites in other alphaviruses to infer where those chains would be split into individual proteins. [1]
A run of A’s within the 3′ region
Sequenced copies had 19, 36, 43, 91, 94 or 106 A’s beginning at the same position.
The length pattern is consistent with slippage. The experiment sequenced copies of the genome, so the enzyme’s behavior was inferred. [1]

How is the internal tract different from the tail?

The two runs occupy different positions. The internal tract lies in an untranslated region near the 3′ end of the RNA. The tail begins at the very end of the sequence. [1]

What does polymerase slippage mean?

A polymerase is an enzyme that copies genetic material. On a repeated sequence, it can lose its place and copy some letters again. The authors suggested that this could explain why the runs shared a starting point but ended up different lengths. [1]

Can untranslated RNA affect how a virus grows?

Untranslated RNA can affect the virus without coding for a protein. Later experiments altered other repeated sequences in chikungunya’s 3′ region and found changes in viral fitness in mosquitoes. Those tests concerned other repeats, so the role of the S27 A run remains open. [1][2]

Original research

  1. Khan et al. (2002), Journal of General Virology. Complete nucleotide sequence of chikungunya virus and evidence for an internal polyadenylation site. Primary S27 genome sequence and comparison of internal A-tract lengths.
  2. Chen et al. (2013), PLOS Pathogens. Chikungunya virus 3′ untranslated region: adaptation to mosquitoes and a population bottleneck as major evolutionary forces. Primary experiments on untranslated-region repeats and fitness.