Decryption of sequence, structure, and functional features of SINE repeat elements in SINEUP non-coding RNA-mediated post-transcriptional gene regulation.

RNA structure folding largely influences RNA regulation by providing flexibility and functional diversity. In silico and in vitro analyses are limited in their ability to capture the intricate relationships between dynamic RNA structure and RNA functional diversity present in the cell. Here, we investigate sequence, structure and functional features of mouse and human SINE-transcribed retrotransposons embedded in SINEUPs long non-coding RNAs, which positively regulate target gene expression post-transcriptionally. In-cell secondary structure probing reveals that functional SINEs-derived RNAs contain conserved short structure motifs essential for SINEUP-induced translation enhancement. We show that SINE RNA structure dynamically changes between the nucleus and cytoplasm and is associated with compartment-specific binding to RBP and related functions. Moreover, RNA-RNA interaction analysis shows that the SINE-derived RNAs interact directly with ribosomal RNAs, suggesting a mechanism of translation regulation. We further predict the architecture of 18 SINE RNAs in three dimensions guided by experimental secondary structure data. Overall, we demonstrate that the conservation of short key features involved in interactions with RBPs and ribosomal RNA drives the convergent function of evolutionarily distant SINE-transcribed RNAs.

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, and which up-regulate the translation of target mRNA. They have been studied in a wide range of applications, as both biological and therapeutic tools, although the underpinning molecular mechanism is unclear. Here, we focused on the sub-cellular distribution of target mRNAs and SINEUP RNAs, performing co-transfection of expression vectors for these transcripts into human embryonic 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 a key phenomenon. 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 employed by regulatory RNAs implicated in efficient protein translation.

Multi-year whole-blood transcriptome data for the study of onset and progression of Parkinson's Disease.

Parkinson's disease (PD) is an age-related, chronic and progressive neurodegenerative disorder characterized by a loss of multifocal neurons, resulting in both non-motor and motor symptoms. While several genetic and environmental contributory risk factors have been identified, more exact methods for diagnosing and assessing prognosis of PD have yet to be established. Here we describe the generation and validation of a dataset comprising whole-blood transcriptomes originally intended for use in detection of blood biomarkers and transcriptomic network changes indicative of PD. Whole-blood samples extracted from both early-stage PD patients and healthy controls were sequenced using no-amplification non-tagging cap analysis of gene expression (nAnT-iCAGE) to analyse differences in global RNA expression patterns across the conditions. Subsequent sampling of a subset of PD patients one-year later provides the opportunity to study changes in transcriptomes arising due to disease progression.