Interaction of the N‐Terminal Tandem Domains of hnRNP LL with the BCL2 Promoter i‐Motif DNA Sequence

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Abstract
The human genome contains GC‐rich sequences able to form tetraplex secondary structures known as the G‐quadruplex and i‐motif. Such sequences are notably present in the promoter region of oncogenes and are proposed to function as regulatory elements of gene expression. The P1 promoter of BCL2 contains a 39‐mer C‐rich sequence (Py39wt) that can fold into a hairpin or an i‐motif in a pH‐dependent manner in vitro. The protein hnRNP LL was identified to recognise the i‐motif over the hairpin conformation and act as an activating transcription factor. Thus, the Py39wt sequence would act as an ON/OFF switch, according to the secondary structure adopted. Herein, a structural study of the interaction between hnRNP LL and Py39wt is reported. Both N‐terminal RNA recognition motifs (RRM12) cooperatively recognise one Py39wt DNA sequence and engage their β‐sheet to form a large binding platform. In contrast, the C‐terminal RRMs show no binding capacity. It is observed that RRM12 binds to Py39wt regardless of the DNA conformation. We propose that RRM12 recognises a single‐stranded CTCCC element present in loop 1 of the i‐motif and in the apical loop of the hairpin conformation.
Funding Information
  • Hessisches Ministerium für Wissenschaft und Kunst (BMRZ)

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