Xiao Ling Li, Lorinc Pongor, Wei Tang, Sudipto Das, Bruna R. Muys, Matthew F. Jones, Sarah B. Lazar, Emily A. Dangelmaier, Corrine C. R. Hartford, Ioannis Grammatikakis, Qinyu Hao, Qinyu Sun, Aaron Schetter, Jennifer L. Martindale, BinWu Tang, Lisa M. Jenkins, Ana I. Robles, Robert L. Walker, Stefan Ambs, Raj Chari, Svetlana A.Shabalina, Myriam Gorospe, Perwez S. Hussain, Curtis C. Harris, Paul S. Meltzer, Kannanganattu V. Prasanth, Mirit I. Aladjem, Thorkell Andresson, and Ashish Lal*

• Submitter: Xiao ling Li (Biologist, bioinformatician, chemist, technician)
• email: lix7@mail.nih.gov

Long noncoding RNAs (lncRNAs) are often associated with polysomes, indicating coding potential. However, only a handful of endogenous proteins encoded by putative lncRNAs have been identified and assigned a function. Here, we report the discovery of a putative gastrointestinal tract-specific lncRNA (LINC00675) that is regulated by the pioneer transcription factor FOXA1 and encodes a conserved small protein of 79 amino acids which we termed FORCP (FOXA1-Regulated Conserved Small Protein). FORCP transcript is undetectable inmost cell types but is abundant in well-differentiated colorectal cancer (CRC) cells where it functions to inhibit proliferation, clonogenicity and tumorigenesis. The epitope-tagged and endogenous FORCP protein predominantly localizes to the endoplasmic reticulum (ER). In response to ER stress, FORCP depletion results in decreased apoptosis. Our findings on the initial characterization of FORCP demonstrate that FORCP is a novel, conserved small protein encoded by a mis-annotated lncRNA that regulates apoptosis and tumorigenicity in well differentiated CRC cells.