Long Noncoding RNA <i>HCP5</i>, a Hybrid HLA Class I Endogenous Retroviral Gene: Structure, Expression, and Disease Associations

• Main Author: Jerzy K. Kulski
• Format: Article
• Language: English
• Published: MDPI AG 2019-05-01
• Series: Cells
• Subjects: HCP5; lncRNA; MHC; HLA; human endogenous retrovirus (HERV); cancer; autoimmune diseases; competing endogenous RNA (ceRNA); human immunodeficiency virus (HIV); human papillomavirus (HPV)
• Online Access: https://www.mdpi.com/2073-4409/8/5/480

The <i>HCP5</i> RNA gene (NCBI ID: 10866) is located centromeric of the <i>HLA-B</i> gene and between the <i>MICA</i> and <i>MICB</i> genes within the major histocompatibility complex (MHC) class I region. It is a human species-specific gene that codes for a long noncoding RNA (lncRNA), composed mostly of an ancient ancestral endogenous antisense 3&#8242; long terminal repeat (LTR, and part of the internal <i>pol</i> antisense sequence of endogenous retrovirus (ERV) type 16 linked to a human leukocyte antigen (HLA) class I promoter and leader sequence at the 5&#8242;-end. Since its discovery in 1993, many disease association and gene expression studies have shown that <i>HCP5</i> is a regulatory lncRNA involved in adaptive and innate immune responses and associated with the promotion of some autoimmune diseases and cancers. The gene sequence acts as a genomic anchor point for binding transcription factors, enhancers, and chromatin remodeling enzymes in the regulation of transcription and chromatin folding. The <i>HCP5</i> antisense retroviral transcript also interacts with regulatory microRNA and immune and cellular checkpoints in cancers suggesting its potential as a drug target for novel antitumor therapeutics.