The human genome contains thousands of non-canonical open reading frames (ORFs) with the potential to encode functional proteins, including microproteins. These unannotated, cryptic proteins are not easily detected by conventional approaches and are considered part of the “dark” proteome.
Previous studies have highlighted the tumor-suppressive function of some microproteins in colorectal cancer (CRC), but their role in cancer remains largely unknown. To provide further insights, researchers led by Yiwen Chen, Ph.D., used an integrated multiomic approach combining ribosome profiling, CRISPR/Cas9 screens and large-scale analysis of clinical data to identify non-canonical ORFs that may be functionally relevant in CRC. They identified a long noncoding RNA-encoded microprotein, SMIMP (SMC1A-interacting microprotein), that has tumor-promoting function in vivo and is associated with poor prognosis.
They discovered that SMIMP plays an important role in gene regulation as part of the cohesin-mediated regulatory network. This study highlights the importance of investigating the functional roles of non-canonical ORFs to find potential new therapeutic targets.