Switchable tetraplex elements in the heterogeneous nuclear ribonucleoprotein K promoter: micro-environment dictated structural transitions of G/C rich elements

Bose, Debopriya (author): Department of Biological Sciences, Bose Institute, West Bengal, Kolkata, India

Banerjee, Nilanjan (author): Department of Biological Sciences, Bose Institute, West Bengal, Kolkata, India

Roy, Ananya (author): Department of Biological Sciences, Bose Institute, West Bengal, Kolkata, India

Sengupta, Pallabi (author): Umeå universitet,Institutionen för medicinsk kemi och biofysik

Chatterjee, Subhrangsu (author): Department of Biological Sciences, Bose Institute, West Bengal, Kolkata, India

(creator_code:org_t)

2024
2024
English.
In: Journal of Biomolecular Structure and Dynamics. - : Taylor & Francis. - 0739-1102 .- 1538-0254.

Related links:: https://urn.kb.se/re...; show more...; https://doi.org/10.1...; show less...

Abstract Subject headings

We have elucidated the hnRNP K promoter as a hotspot for tetraplex-based molecular switches receptive to micro-environmental stimuli. We have characterised the structural features of four tetraplex-forming loci and identified them as binding sites of transcription factors. These segments form either G-quadruplex or i-motif structures, the structural dynamicity of which has been studied in depth via several biophysical techniques. The tetraplexes display high dynamicity and are influenced by both pH and KCl concentrations in vitro. The loci complementary to these sequences form additional non-canonical secondary structures. In the cellular context, the most eminent observation of this study is the binding of hnRNP K to the i-motif forming sequences in its own promoter. We are the first to report a probable transcriptional autoregulatory function of hnRNP K in coordination with higher-order DNA structures. Herein, we also report the positive interaction of the endogenous tetraplexes with Sp1, a well-known transcriptional regulator. Treatment with tetraplex-specific small molecule ligands further uncovered G-quadruplexes’ functioning as repressors and i-motifs as activators in this context. Together, our findings strongly indicate the critical regulatory role of the identified tetraplex elements in the hnRNP K promoter. Communicated by Ramaswamy H. Sarma.

By the author/editor: Bose, Debopriya; Banerjee, Nilanj ...; Roy, Ananya; Sengupta, Pallab ...; Chatterjee, Subh ...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

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