Investigation of LINC00493/SMIM26 Gene Suggests Its Dual Functioning at mRNA and Protein Level

Abstract

The amount of human long noncoding RNA (lncRNA) genes is comparable to protein-coding; however, only a small number of lncRNAs are functionally annotated. Previously, it was shown that lncRNAs can participate in many key cellular processes, including regulation of gene expression at transcriptional and post-transcriptional levels. The lncRNA genes can contain small open reading frames (sORFs), and recent studies demonstrated that some of the resulting short proteins could play an important biological role. In the present study, we investigate the widely expressed lncRNA LINC00493. We determine the structure of the LINC00493 transcript, its cell localization and influence on cell physiology. Our data demonstrate that LINC00493 has an influence on cell viability in a cell-type-specific manner. Furthermore, it was recently shown that LINC00493 has a sORF that is translated into small protein SMIM26. The results of our knockdown and overexpression experiments suggest that both LINC00493/SMIM26 transcript and protein affect cell viability, but in the opposite manner.

LINC00493‐encoded microprotein SMIM26 exerts anti‐metastatic activity in renal cell carcinoma

“…A recent study observed that knockdown of LINC00493 slightly inhibited cell growth in A375 and MDA‐MB‐231 cell lines (Konina et al , 2021), indicating that LINC00493 is functional and activated in mammalian cells. Our earlier works dedicated to the global discovery of new smORFs by using full‐length translating mRNA sequencing and ribosome profiling (Wang et al , 2013), and reported a total of 314 lncRNA‐encoded new microproteins (Lu et al , 2019).…”

“…SMIM26, one of the microproteins identified in our previous study, was reported to be involved in the regulation of cell viability (Konina et al , 2021; Yeasmin et al , 2021). In this study, we validated that microprotein SMIM26 was derived from lncRNA LINC00493 and resided in mitochondria.…”