Research and Development

Background

Long and small non-coding RNAs represent a large portion of the human transcriptome with yet poorly identified functions.
Among them, small interference RNAs and micro RNAs represent well-studied classes of RNAs that inhibit gene expression and are currently explored for their application as RNA therapeutics.
A fraction of long non-coding RNAs participates in antisense pairing with sense
protein-coding transcripts.

We have recently discovered a new class of antisense long non-coding RNAs (SINEUPs) that promotes translation of partially overlapping sense coding mRNAs with no effects on RNA levels.


Table 1


SINEUPs are made of two functional domains: one overlaps with the protein-coding target (or Target Antisense Sequence or TAS) and the other one functions as activator of translation (or Protein Activation Sequence or PAS).
The TAS is usually centered around the ATG of coding partner mRNA, but minimal sequence overlap is sufficient to determine target selection.
The PAS contains a retrotransposon-derived sequence of the SINEB2 (Short Interspersed Nuclear Element B2) family that loads the coding mRNA to polysomes
for efficient translation.
By swapping Target Antisense Sequences (TAS), SINEUPs molecules can increase protein synthesis of your gene of interest.

Table 3


Applications

Biotechnology

SINEUPs are tools to increase protein synthesis of any gene of interest in mammalian cells. Biotechnology applications of SINEUPs will range from basic research to large-scale industrial production of recombinant proteins including antibodies.

Therapeutics

SINEUPs can be used to alter protein expression in vivo of endogenous target genes involved in disease. Therapeutic applications of SINEUPs can include the increase of pro-apoptotic proteins (as anti-cancer drugs) or pro-survival proteins (as neuroprotective drug). Additionally, SINEUPs may overcome the limiting protein levels in haploinsufficiences.

Illustrations by Davide Zarli