Regulation of the 3’ UTR in BDNF mRNA at the DNA Level

Abstract

Brain-derived neurotrophic factor (BDNF) is part of the neurotrophic family of genes that encodes for proteins that are known to promote survival of neurons in the peripheral and central nervous systems. The expression of the BDNF gene results in the production of two mRNAs with different lengths, one with a short 3’ untranslated region (UTR) and the second with a long 3’ -UTR, which are believed to serve different functionalities. The ratio of long to short 3’ -UTR in BDNF mRNA changes in different regions of the brain. The long 3’ -UTR mRNA is found in both dendrites and soma, whereas the short 3’ -UTR is only found in the soma, implying that the BDNF mRNA with the long 3’ -UTR is involved in maintaining the neuroplasticity of the brain. Thus, the regulation of the BDNF 3’ -UTR length is important, and it may be achieved at the DNA level, at the mRNA level or both. In this study we are investigating the potential of a 20 nucleotide DNA sequence located in the BDNF gene to adopt non-canonical G quadruplex and i-motif structures that might be involved in regulating the production of long versus short length BDNF mRNA 3′-UTR.