Despite recent efforts in discovering novel long non-coding RNAs (lncRNAs) and 
unveiling their functions in a wide range of biological processes their 
applications as biotechnological or therapeutic tools are still at their 
infancy. We have recently shown that AS Uchl1, a natural lncRNA antisense to the 
Parkinson's disease-associated gene Ubiquitin carboxyl-terminal esterase L1 
(Uchl1), is able to increase UchL1 protein synthesis at post-transcriptional 
level. Its activity requires two RNA elements: an embedded inverted SINEB2 
sequence to increase translation and the overlapping region to target its sense 
mRNA. This functional organization is shared with several mouse lncRNAs 
antisense to protein coding genes. The potential use of AS Uchl1-derived lncRNAs 
as enhancers of target mRNA translation remains unexplored. Here we define AS 
Uchl1 as the representative member of a new functional class of natural and 
synthetic antisense lncRNAs that activate translation. We named this class of 
RNAs SINEUPs for their requirement of the inverted SINEB2 sequence to 
UP-regulate translation in a gene-specific manner. The overlapping region is 
indicated as the Binding Doman (BD) while the embedded inverted SINEB2 element 
is the Effector Domain (ED). By swapping BD, synthetic SINEUPs are designed 
targeting mRNAs of interest. SINEUPs function in an array of cell lines and can 
be efficiently directed toward N-terminally tagged proteins. Their biological 
activity is retained in a miniaturized version within the range of small RNAs 
length. Its modular structure was exploited to successfully design synthetic 
SINEUPs targeting endogenous Parkinson's disease-associated DJ-1 and proved to 
be active in different neuronal cell lines. In summary, SINEUPs represent the 
first scalable tool to increase synthesis of proteins of interest. We propose 
SINEUPs as reagents for molecular biology experiments, in protein manufacturing 
as well as in therapy of haploinsufficiencies.