Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative disease that causes the degradation of neurons in the spinal cord, cerebral cortex, and brain stem. There is currently no cure for ALS and the average survival rate is 3-5 years after diagnosis. Recently, a number of studies have proposed that dysregulated levels of microRNAs (miRNAs) may link ALS and other neurodegenerative diseases. miRNAs are small, noncoding RNAs that play a key role in gene expression and cell growth, controlling cellular functions such as transcriptional regulation, mRNA cleavage, and translation repression. Mature miRNAs are 20-24 nucleotide long being processed from premature miRNAs (pre-miRNAs), which undergo enzymatic cleavage by the endonuclease Dicer. Within guanine-rich pre-miRNAs, secondary structures called G-quadruplexes can form, interfering with their maturation by Dicer. Furthermore, the RNA-binding protein FMRP contains the arginine-glycine-glycine specific recognition motifs that is known to bind with high affinity to G-quadruplexes. Recent research determined that a specific miRNA sequence, miRNA-1249, is dysregulated in both ALS mouse models and human ALS patients. Here we investigated if a G-quadruplex is forming within the G-rich pre-miR-1249 by using various biophysical techniques including <sup>1</sup>H-NMR spectroscopy, CD spectroscopy, UV thermal denaturation, and gel electrophoresis. Moreover, we investigated if this G quadruplex structure could affect the pre-miR-1249 maturation by Dicer and potentially through its interactions with FMRP.

Investigation of G-quadruplex structure formation within pre-miR-1249

2019 Spring National Meeting

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