Biology subjects

Zucchelli, S.

Publications and source records attributed to Zucchelli, S..

2 recordsLinked to original sources

bioRxiv2023

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

SINEUPs are antisense long non-coding RNAs that enhance translation of overlapping sense mRNAs through the activity of two domains: a SINEB2 sequence UP-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 SINEUP AS Uchl1 RNA is an Internal Ribosomal Entry Site (IRES) when acting in cis and 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-coding circ5533, transcribed from the c-myc locus, enhances endogenous protein expression of its target PX 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.

molecular biology↗

bioRxiv2019

SINEUP long non-coding RNA acts via PTBP1 and HNRNPK to promote translational initiation assemblies

SINEUPs are long non-coding RNAs (lncRNAs) that contain a SINE element, which up-regulate the translation of target mRNA and have been studied in a wide range of applications for biological and therapeutic tools, although the molecular mechanism is unclear. Here, we focused on the kinetic distribution of target mRNAs and SINEUP RNAs by performing co-transfection of expression vectors for these transcripts into human embryonic normal kidney cells (HEK293T/17) to investigate the network of translational regulation. The results showed that co-localization of target mRNAs and SINEUP RNAs in the cytoplasm was one of the key phenomena. We identified PTBP1 and HNRNPK as essential RNA binding proteins. These proteins contributed to SINEUP RNA sub-cellular distribution and to assembly of translational initiation complexes, leading to enhanced target mRNA translation. These findings will promote a better understanding of the mechanisms on the fate of regulatory RNAs implicated in efficient protein translation.

molecular biology↗