Orphan riboswitches

Orphan riboswitch candidates are noncoding RNA motifs whose representatives are believed to function as genetic regulatory elements; however, their specific ligands remain unidentified. In this section, we present a list of 30 orphan riboswitch candidates to draw attention to their most distinctive characteristics. The significance and quality of a riboswitch candidate can be assessed by considering the number of representatives discovered, the complexity displayed by its conserved sequence and secondary structure, and its associations with diverse gene types. We categorize these candidates as either strong or weak orphan riboswitch candidates based on the criterion, the strength of the characteristics of candidates listed above. This section was adapted from the work of Ron Breaker primarily[1]

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Strong orphan riboswitches

Consensus sequence and secondary structure model for the strong orphan riboswitch candidates[1].


Riboswitch orphan riboswitch
Name Rfam ID Unique representatives Conserved nucleotides Top genes (>10%)
ykkC 2c[2-5] None 45 66 nudix hydrolase
ykkC 2d[2-5] None 144 38 possible transporters of unknown specificity (phn_DUF6)
speF[6] RF00518 868 92 (59) Ornithine decarboxylase
serC[6] RF00517 1274 16 phosphoserine aminotransferase
ybhL[6] RF00520 207 26 possible transporter of unknown specificity
ATPC[7] RF01067 222 15 ATP synthase component
sucA[7] RF01070 490 16 2-oxoglutarate dehydrogenase component
sucA-II[8] RF01758 294 25 2-oxoglutarate dehydrogenase component
aceE[8] None 181 12 pyruvate dehydrogenase component
gabT[8] RF01738 315 21 (23) γ-aminobutyric acid transaminase
icd[8] RF04189 373 14 isocitrate dehydrogenase isozyme II
Lacto-usp[8] RF01710 63 58 protein of unknown function
manA[8] RF01745 527 14 (15, 19) sugar pathways, various others
Moco-II[8] RF01713 20 12 molybdenum-binding proteins, others
msiK[8] RF01747 1124 23 component of transporters
potC[8] RF01751 221 8 peroxiredoxin, thiamin related proteins
psaA[8] RF01752 76 52 photosystem I component
Pseudomon-GGDEF[8] None 65 67 signal protein of unknown function
SAM-Chlorobi[8] RF01724 40 22 S-adenosylmethionine synthase
wcaG[8] RF01761 137 13 NAD-dependent epimerase or hydratase

Weak orphan riboswitches

Consensus sequence and secondary structure model for the weak orphan riboswitch candidates[1].


Ribozyme applications
Name Rfam ID Unique representatives Conserved nucleotides Top genes (>10%)
sucC[8] None 72 25 succinyl-CoA synthetase component
rmf[8] RF01755 363 50 ribosomal modulation factor
Termite-flg[8] RF01729 67 18 flagellin proteins
nuoG[8] RF01748 38 24 (49) NADH-ubiquinone oxidoreductase component
livK[8] RF01744 88 33 Protein of unknown function
Polynucleobacter-1 [8] None 86 19 unclear


[1] Challenges of ligand identification for the second wave of orphan riboswitch candidates.
Greenlee, E. B. et al.
RNA Biol. 15, 377–390 (2018).

[2] Riboswitches for the alarmone ppGpp expand the collection of RNA-based signaling systems.
Sherlock, M. E., Sudarsan, N. & Breaker, R. R.
Proc. Natl. Acad. Sci. U. S. A. 115, 6052–6057 (2018).

[3] Tandem riboswitches form a natural Boolean logic gate to control purine metabolism in bacteria.
Sherlock, M. E., Sudarsan, N., Stav, S. & Breaker, R. R.
Elife 7, (2018).

[4] New RNA motifs suggest an expanded scope for riboswitches in bacterial genetic control.
Barrick, J. E. et al.
Proc. Natl. Acad. Sci. U. S. A. 101, 6421–6426 (2004).

[5] Metabolism of Free Guanidine in Bacteria Is Regulated by a Widespread Riboswitch Class.
Nelson, J. W., Atilho, R. M., Sherlock, M. E., Stockbridge, R. B. & Breaker, R. R.
Mol. Cell 65, 220–230 (2017).

[6] Evidence for a second class of S-adenosylmethionine riboswitches and other regulatory RNA motifs in alpha-proteobacteria.
Corbino, K. A. et al.
Genome Biol. 6, R70 (2005).

[7] Identification of 22 candidate structured RNAs in bacteria using the CMfinder comparative genomics pipeline.
Weinberg, Z. et al.
Nucleic Acids Res. 35, 4809–4819 (2007).

[8] Comparative genomics reveals 104 candidate structured RNAs from bacteria, archaea, and their metagenomes.
Weinberg, Z. et al.
Genome Biol. 11, R31 (2010).