SMIM36, a novel and conserved microprotein, is involved in retinal lamination in zebrafish.

Microproteins are small proteins comprising 2 to 200 amino acids, arising from small Open Reading Frames (smORFs). They are found in different parts of the cell and regulate basic molecular processes like DNA replication, repair, transcription and recombination. SMIM or SMall Integral Membrane proteins are novel, largely uncharacterized, members to the class of microproteins defined by the presence of a transmembrane domain. The retinal transcriptome of zebrafish, reported previously by our group, revealed several novel mRNA transcripts that show oscillating expression in a diurnal manner. Here, we show that one of these transcripts encodes the zebrafish homolog of the human SMIM36 protein, which has not been functionally characterised. This highly conserved microprotein is expressed in the human and zebrafish retina, and efficiently translated in cell lines. Using single-cell RNA-seq datasets, we found that it is expressed in the bipolar cells, rods and Muller glia in the human retina. The knockdown of SMIM36 using splice-block morpholino caused microphthalmia and defects in the retinal layers in zebrafish. Therefore, we show the role of a microprotein in the neural retina thus paving the way for future studies on the role of SMIM proteins in retinal disorders.