HAR1MC · Structure determination of human and chimpanzee HAR1F RNA by NMR

The 118-nt long human accelerated region 1 of humans (hHAR1F) possesses the largest genetic drift of all 49 so far identified HARs with an estimated 18 substitutions in comparison to the homologous sequence from the chimpanzee (cHAR1F). In order to understand the unknown function of these non-coding RNAs in the development of human consciousness it is essential to elucidate their secondary and tertiary structures of the HAR RNA with atomic resolution. We will design RNA constructs which will mimic sub-domains of the whole cHAR1F and hHAR1F regions. Afterwards we will biochemically prepare these RNA constructs. On the basis of NMR spectroscopic investigations of these RNAs (resonance assignment, measurement of RDC data, 13C-relaxation and relaxation dispersion) we will determine models for the tertiary structures and study their dynamics. Individual mutations of the cHAR1F sequence toward the human sequence will give information, which of the 18 substitutions triggers the change in conformation found in hHAR1F RNA. The knowledge of the functions of the cHAR1F and hHAR1F RNA could give an explanation about the cerebral cortex development of humans in comparison to that of the chimpanzee and make a contribution to understanding which determinants are characteristic for the humans.