RNAi and Ino80 complex control rate limiting translocation step that moves rDNA to eroding telomeres

Area of Science:

• Genetics
• Molecular Biology
• Chromosomal Biology

Background:

• Canonical telomeres protect chromosome ends, but alternative mechanisms exist.
• HAATIrDNA represents a telomerase-negative survival mode using ribosomal DNA (rDNA) repeats at chromosome ends.

Purpose of the Study:

• To elucidate the mechanism of HAATIrDNA formation and the roles of RNAi and Ino80C.
• To investigate the relationship between RNAi and Ino80C in controlling translocation events.

Main Methods:

• Genetic analysis of translocation events.
• Investigating the requirement for RNAi and Ino80C in HAATIrDNA formation.
• Characterizing the dual roles of Dcr1 and Iec1 in HAATI subtype choice.

Main Results:

• HAATIrDNA formation initiates with a single translocation of rDNA from Chr III to subtelomeric elements (STE) on Chr I or II, dependent on RNAi and Ino80C.
• The STE-rDNA junction is then propagated to other STE chromosome ends independently of RNAi or Ino80C.
• Dcr1 (RNAi) and Iec1 (Ino80C) exhibit dual roles, promoting HAATIrDNA but inhibiting the rare HAATISTE subtype.

Conclusions:

• RNAi and Ino80C are crucial for initiating HAATIrDNA formation through a specific translocation event.
• These pathways exhibit crosstalk, with components playing dual roles in regulating different HAATI subtypes.
• This study reveals an unappreciated interplay between RNAi and Ino80C in managing unusual chromosomal end formations.