Structural RNA has lower folding energy than random RNA of the same dinucleotide frequency

Abstract

We present results of computer experiments that indicate that several RNAs for which the native state (minimum free energy secondary structure) is functionally important (type III hammerhead ribozymes, signal recognition particle RNAs, U2 small nucleolar spliceosomal RNAs, certain riboswitches, etc.) all have lower folding energy than random RNAs of the same length and dinucleotide frequency. Additionally, we find that whole mRNA as well as 5-UTR, 3-UTR, and cds regions of mRNA have folding energies comparable to that of random RNA, although there may be a statistically insignificant trace signal in 3-UTR and cds regions. Various authors have used nucleotide (approximate) pattern matching and the computation of minimum free energy as filters to detect potential RNAs in ESTs and genomes. We introduce a new concept of the asymptotic Z-score and describe a fast, whole-genome scanning algorithm to compute asymptotic minimum free energy Z-scores of moving-window contents. Asymptotic Z-score computations offer another filter, to be used along with nucleotide pattern matching and minimum free energy computations, to detect potential functional RNAs in ESTs and genomic regions.

Searching for IRES

“…Although distinct ordered structures may exist, the overall degree of secondary structure as measured by the lowest free energy of possible folds of noncoding regions of mRNA was not seen to be different from random sequence or from coding sequence (Workman and Krogh 1999;Rivas and Eddy 2000;Clote et al 2005). …”

Computational methods in noncoding RNA research

“…RNAZ [148], a development of RNAalifoldz [147], is a Support Vector Machine classifier that uses two scores to classify multiple alignments as ncRNA or not: z-scores 23 of the individual sequences from the input alignment and a structure conservation index (SCI). The last is given by E A /E, where E A is the alignment thermodynamic score given by the RNAalifold and E is the average free energy of the individual sequences (given by the RNAfold).…”

“…Since the program outputs the free-energy of the alignment, this can be used to calculate the alignment's 22 We can say that "other" means "I have no idea". 23 The z-score computation needs the average and standard deviation of the scores of negative sequences. Often, these measures are calculated using shufflings of the input sequence.…”

“…It was used to show that, although some ncRNAs do not have a significant lower energy, precursor microRNAs do have. Posterior work [23] showed that other ncRNAs can also be detected by the significance of their folding energy.…”

Prediction of structured non-coding RNAs in the genomes of the nematodesCaenorhabditis elegans andCaenorhabditis briggsae

“…RNAs that are under long-time selection for secondary structure can be expected to have sequences that are more resilient against mutations (Wagner and Stadler, 1999;Nimwegen et al, 1999), which in turn correlates with increased thermodynamic stability of the fold. Indeed, it has been observed that functional RNAs are more stable than the structures formed by randomized sequences (Bonnet et al, 2004;Washietl and Hofacker, 2004;Clote et al, 2005). The program RNAz (Washietl et al, 2005a) combines both approaches.…”