Oral Presentation 16th Asian Conference on Transcription 2019

Heterochromatin Protein 1α interacts with parallel RNA and DNA G-quadruplexes (1093)

Tracy Hale 1 , Ruby Roach 1 , Vyacheslav Filichev 1 , Geoffery Jameson 1 , Carlos Gonzalez 2
  1. Massey University, Palmerston North, MANAWATU, New Zealand
  2. Instituto de Química Física ‘Rocasolano’, CSIC, Madrid, Spain

The maintenance of telomeric heterochromatin is essential to genome integrity as it protects the ends of chromosomes from degradation and the DNA damage response machinery.  In mammals, telomeres comprise of highly conserved tandem repeats of (TTAGGG)n terminating in a 3' overhang.  Transcription from these repeats results in TERRA transcripts of heterogeneous lengths with the majority consisting of UUAGGG tracks that are shorter than 400 bases.  These guanine-rich transcripts form G-quadruplex (G4) structures by the association of four guanines bound through Hoogsteen hydrogen bonding.  While it has been known for some time that DNA and RNA can form non-B structures in vitro, only recently has it been demonstrated that G4 and intercalated C-rich motif (i-motif) structures exist in vivo and contribute to genome function.  The presence of TERRA within the telomere nucleoprotein complex is proposed to act as a docking site for proteins involved in telomere function including Heterochromatin Protein 1α (HP1α).

To identify if the interaction of HP1α with RNA is structure dependent, we investigated whether HP1α recognises the G4 structures formed by TERRA.  We found that the hinge region of HP1α binds with high affinity not only the TERRA G4 structures of parallel topology but also DNA G4 structures of the same topology.  This suggests not only a mechanism by which TERRA expression can promote heterochromatin formation at telomeres, but the formation of G4s within the genome could influence HP1α function in gene silencing, RNA processing or DNA repair.