Retrotransposon addiction promotes centromere function via epigenetically activated small RNAs

Area of Science:

• Epigenetics
• Molecular Biology
• Genetics

Background:

• Centromeric retrotransposons play a role in eukaryotic centromere evolution.
• The function of centromeric retrotransposons, particularly in centromere function, remains largely unknown.
• In Arabidopsis, centromeric ATHILA retrotransposons generate small interfering RNAs in mutants lacking DECREASE IN DNA METHYLATION1 (DDM1).

Purpose of the Study:

• To investigate the role of centromeric retrotransposons and small RNAs in centromere function and chromosome segregation.
• To elucidate the interplay between DECREASE IN DNA METHYLATION1 (DDM1) and RNA-dependent RNA polymerase in maintaining genome stability.
• To understand the epigenetic inheritance of centromeric defects.

Main Methods:

• Analysis of mutants lacking DDM1 and RNA-dependent RNA polymerase.
• Observation of chromosome segregation during mitosis.
• Epigenetic rescue experiments using artificial small RNAs targeting ATHILA5 retrotransposons.
• Comparative analysis with fission yeast and human systems.

Main Results:

• Mutants lacking both DDM1 and RNA-dependent RNA polymerase exhibit developmental defects and chromosome 5 mis-segregation.
• Fertility and segregation defects are epigenetically inherited with centromere 5.
• Artificial small RNAs targeting ATHILA5 retrotransposons can rescue these defects.
• Epigenetically activated small RNAs are crucial for pericentromeric condensation, chromosome cohesion, and mitotic chromosome segregation.

Conclusions:

• Centromeric ATHILA retrotransposons silence transcription while making centromere function reliant on retrotransposon small RNAs in the absence of DDM1.
• This mechanism is conserved across eukaryotes, with parallels in yeast and human chromosome segregation.
• Epigenetic regulation by small RNAs is vital for centromere integrity and genome stability.