: Hypothetical Proteins [HP] are the transcripts predicted to be expressed in an organism but no evidence of it exists in gene banks. On the other hand, long non-coding RNAs [lncRNAs] are the transcripts that might be present in the 5’ UTR or intergenic regions of the genes whose length are above 200 bases. With the known unknown [KU] regions in the genomes rapidly existing in gene banks, there is a need to understand the role of open reading frames in context of annotation. In this commentary, we emphasize that HPs could indeed be the predecessors of lncRNAs.

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