Biology subjects

Scarpato, M.

Publications and source records attributed to Scarpato, M..

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↗

bioRxiv2020

The piRNA pathway sustains adult neurogenesis by repressing protein synthesis

Adult Neural progenitor cells (aNPCs) ensure lifelong neurogenesis in the mammalian hippocampus. Proper regulation of aNPC fate entails important implications for brain plasticity and healthy aging. Piwi proteins and the small noncoding RNAs interacting with them (piRNAs) are best known in gonads as repressors of transposons. Here, we show that Piwil2 (Mili) and piRNAs are abundant in aNPCs of the postnatal mouse hippocampus and demonstrate that this pathway is essential for proper neurogenesis. Particularly, depleting the piRNA pathway in aNPCs impaired neurogenesis, increased senescence and accordingly the generation of reactive glia. Moreover, this manipulation primarily elevated 5S ribosomal RNA, SINEB1 and mRNAs encoding ribosomal proteins and regulators of translation, resulting in higher polysome density and protein synthesis upon differentiation. Our results provide evidence of an essential role for the piRNA pathway in maintaining homeostasis to sustain neural stem cell fate, underpinning its possible involvement in brain plasticity and successful aging.

neuroscience↗