Brain cytoplasmic 200 long-noncoding RNA (or BC200 lncRNA) is a 200 nucleotide RNA transcript found predominantly in the brain with a primary function of regulating translation by inhibiting its initiation. As a long non-coding RNA, it belongs to a family of RNA transcripts that are not translated into protein (ncRNAs). Of these ncRNAs, lncRNAs are transcripts of 200 nucleotides or longer and are almost three times more prevalent than protein-coding genes. Nevertheless, only a few of the almost 60,000 lncRNAs have been characterized, and little is known about their diverse functions (transcriptional interference, chromatin remodeling, splicing, translation regulation, interaction with miRNAs and siRNAs, and mRNA degradation). BC200 is one lncRNA that has given insight into their specific role in translation regulation, and implications in various forms of cancer as well as Alzheimer's disease.
The accepted gene symbol for the BC200-coding gene is BCYRN1, for Brain cytoplasmic RNA 1.
Characteristics
A repeat polymorphism of cytosines and adenines (CA) was found to be near BCYRN1 and was used as a reference for mapping the gene. Linkage mapping and radiation hybrid mapping localized the BCYRN1 gene to chromosome 2p16.
As a long non-coding cytoplasmic RNA, BC200 RNA is a part of the largest group of non-coding transcripts in the human genome, which is more prevalent than protein coding genes. The 5' region (left arm) of monomeric Alu short interspersed repetitive elements (SINEs) allows for BC200 RNA transposition and has been evolutionarily conserved in other primates. Of this group of SINEs, BC200 is one of few that are transcriptionally active. In humans, it is found in neuropil areas which are composed of predominantly unmyelinated dendrites, axons, and glial cells.
Similarly, the functional analog of BC200 RNA in rodents (BC1 RNA) is expressed largely in somatodendritic domains of the nervous system, making it an ideal model for experimentation. One large difference is in origin; BC200 emerged from retrotransposed Alu domain, while BC1 originated from retrotransposed tRNAAla. Although they evolved separately, both are not usually expressed in non-neural somatic cells, with the exception of tumors.
Structure
The BC200 RNA is the product of an unprocessed monomeric Alu sequence. It is 200 nucleotides long and non-translatable.
BC200 has three distinct structural domains. The 5' region of the RNA defines one domain and consists of Alu repeat elements. The other two structural domains are a central A-rich region, and a C-rich 3' region specific to BC200. The 5' end of this molecule has both primary and secondary structure that is very similar to 7SL RNA, a signal recognition particle RNA (SRP) which also includes a 5' Alu domain.
The BC200 RNA gene has two pseudogenes: BC200 beta and BC200 gamma. These two pseudogenes each have a single gene in the genome, located on separate chromosomes. The beta pseudogene is composed of a BC200 RNA gene and additional Alu sequences. The gamma pseudogene contains an inverted long interspersed nuclear element (LINE). They both have transpositional ability, but the exact mechanism is unknown.
Biosynthesis
The biosynthesis of BC200 RNA occurs at the cell body of a neuron and requires upstream promoter elements, downstream internal promoter elements (intragenic A and B boxes), at least two transcription factor binding sites, a TATA-like sequence, TATA-box binding protein (TBP), and RNA polymerase III.
There is a deletion of sequences between -100 and -1 in the DNA that blocks transcription activity, revealing that the transcription complex must interact with this 100-bp sequence of the upstream region for proper synthesis of BC200 RNA. The TATA-box binding protein (TBP) binds here, and when inhibited, BC200 RNA levels decrease, indicating that the 100 base pair region and TBP are critical players in the biosynthesis of BC200 RNA.
In addition to upstream elements, there is an upstream TATGAAA sequence (similar to TATA box sequence) at positions -28 to -22 which, when deleted, compromises transcription, revealing this TATA-like sequence as another critical player in the synthesis of BC200 RNA. However, transcription is not dependent on the TATA-box binding protein binding to the TATA-like sequence.