Abstract
In addition to its characteristics as a DNA binding transcription factor, HMGA1a is known to bind RNA, sequence specifically and regulate aberrant splicing of the Presenilin-2 gene in sporadic Alzheimer’s disease^1,2^. We show here that an RNA cis-element, immediately upstream the HMGA1a binding site, induces exon inclusion upon mutating a GU sequence to CA. Psoralen mediated UV crosslinking showed U1 snRNP did not bind this sequence but oligonucleotide-mediated RNase H digestion showed it important for U1 snRNP to recognize the authentic 5’ splice site. This sequence (5’-AAGUAC-3’) was tested for hnRNPA1 binding and function. Coimmunoprecipitation of endogenous HMGA1a and hnRNPA1 in HeLa nuclear extract, implicated hnRNPA1 to be involved in HMGA1a mediated dysfunction of U1 snRNP. Though hnRNPA1 binding was weak, there was decreased binding when GU was mutated to CA. hnRNPA1 alone had no effect of splicing of a 5’ splice site adjacently downstream the HMGA1a binding site, but significantly attenuated HMGA1a mediated splicing suppression of this 5’ splice site. Thus, hnRNPA1, known as the human homolog of hrp48 in the PSI model, attenuates HMGA1a mediated U1 snRNP dysfunction.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ohe, K., Manabe, T., Katayama, T. et al. An RNA cis-element upstream of the HMGA1a binding site affects exon exclusion caused by HMGA1a. Nat Prec (2009). https://doi.org/10.1038/npre.2009.4119.1
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/npre.2009.4119.1