BC200 (BCYRN1) - The shortest, long, non-coding RNA associated with cancer

Abstract

With the discovery that the level of RNA synthesis in human cells far exceeds what is required to express protein-coding genes, there has been a concerted scientific effort to identify, catalogue and uncover the biological functions of the non-coding transcriptome. Long, non-coding RNAs (lncRNAs) are a diverse group of RNAs with equally wide-ranging biological roles in the cell. An increasing number of studies have reported alterations in the expression of lncRNAs in various cancers, although unravelling how they contribute specifically to the disease is a bigger challenge. Originally described as a brain-specific, non-coding RNA, BC200 (BCYRN1) is a 200-nucleotide, predominantly cytoplasmic lncRNA that has been linked to neurodegenerative disease and several types of cancer. Here we summarise what is known about BC200, primarily from studies in neuronal systems, before turning to a review of recent work that aims to understand how this lncRNA contributes to cancer initiation, progression and metastasis, along with its possible clinical utility as a biomarker or therapeutic target.

Keywords: BC200; BCYRN1; Cancer; Long non-coding RNA; RNA-protein interactions; Translational regulation; lncRNA.

Fig. 1

Schematic representation of human BC200 promoter region, secondary structure and sequence similarity to 7SL and BC 1 RNAs. (A) The BC200 promoter is divided into three domains. The first is transcription factor (TF) binding site I located between position −100 and −36 bp. The second is TF binding site II located between −35 bp and −6 bp, which contains a TATA box. The binding of TFs to this region is dependent on the third domain, containing two internal promoter elements, A box and B box. TATA binding protein (TBP) binds to the BC200 promoter in the region located between −100 bp to 30 bp [38]. Additional transcription factors that influence the BC200 promoter are not shown. (B) Folding parameters of BC200 RNA (accession number NR038088.1) were determined by mFold [156] and used in forna, an RNA secondary structure visualization tool [157]. Structural elements are colour-coded as follows: Green – stems (canonical helices); red – multiloops/junctions; yellow – interior loops; blue – hairpin loops; orange – 3′ unpaired region. The Alu-like, A-rich and unique regions of BC200 are indicated. (C) Pairwise alignment of BC200 with 7SL (human; accession number X04248.1) and BC1 (mouse; accession number NR001568.1) using MultiAlin [158]. Nucleotides are coloured blue if they are identical between two of the three RNAs; red indicates identical nucleotides among the three non-coding RNAs.

Fig. 2

Expression of BC200 in association with disease contexts. BC200 lncRNA has been linked to many human diseases, mostly through observed alterations to its RNA expression levels in normal versus affected tissue or tumour (Table 2). To fully understand how BC200 can affect cells and influence diseases, detailed examination of its biological roles in each disease context is required. This will require biochemical characterisation of BC200's molecular interactions and experimental determination of how these interactions directly influence cellular processes.