Di Carlo, V. | Search bioRxiv

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

Gene regulatory architectures dissect the evolutionary dynamics of regulatory elements in humans and non-human primates

To gain insight into the evolution of the epigenetic regulation of gene expression in primates, we extensively profiled a new panel of human, chimpanzee, gorilla, orangutan, and macaque lymphoblastoid cell lines (LCLs), using ChIP-seq for five histone marks, ATAC-seq and RNA-seq, further complemented with WGS and WGBS. We annotated regulatory elements and integrated chromatin contact maps to define gene regulatory architectures, creating the largest catalog of regulatory elements in primates to date. We report that epigenetic conservation and its correlation with sequence conservation in primates depends on the activity state of the regulatory element. Our gene regulatory architectures reveal the coordination of different types of components and highlight the role of promoters and intragenic enhancers in the regulation of gene expression. We observed that most regulatory changes occur in weakly active intragenic enhancers. Remarkably, novel human-specific intragenic enhancers with weak activities are enriched in human-specific mutations. These elements appear in genes with signals of positive selection, tissue-specific expression and particular functional enrichments, suggesting that the regulatory evolution of these genes may have contributed to human adaptation.

evolutionary biology↗