Internal Ribosome Entry Sites act as Effector Domain in linear and circular antisense long non-coding SINEUP RNAs

Abstract

SummarySINEUPs are antisense long non-coding RNAs that enhance translation of overlapping sense mRNAs through the activity of two domains: aSINEB2 sequenceUP-regulating translation (Effector Domain, ED) and an antisense region providing target specificity (Binding Domain, BD). In this study, we demonstrate that the invSINEB2 sequence from the natural SINEUPAS Uchl1RNA is an Internal Ribosomal Entry Site (IRES) when acting incisand that known viral and cellular IRES sequences can act as Effector Domain in synthetic SINEUPs.To identify natural IRES-containing, non-coding RNAs with SINEUP-like activity, we focused on circular RNAs showing that the non-codingcirc5533, transcribed from thec-myc locus, enhances endogenous protein expression of its targetPX Domain Containing Serine/Threonine Kinase Like(Pxk)by increasing mRNA association to polysomes.In summary, this study shows that natural and synthetic SINEUPs include linear and circular transcripts with an embedded IRES sequence as ED.