Active Alu retrotransposons in the human genome

Area of Science:

• Genomics
• Molecular Biology
• Evolutionary Biology

Background:

• Alu retrotransposons, originating from 7SL RNA, have expanded significantly in primate genomes, with over a million copies in humans.
• Some Alu copies remain mobile, contributing to genetic variation and disease by inserting into new genomic locations.
• The exact number of active Alu copies and the specific subfamilies responsible remain largely unknown.

Purpose of the Study:

• To conduct a comprehensive functional analysis of Alu copies across the human genome.
• To determine the abundance of active Alu elements and identify which subfamilies harbor them.
• To elucidate the key determinants of Alu retrotransposon activity.

Main Methods:

• Cloning of Alu copies from diverse genomic locations.
• Functional testing of cloned Alu copies using a plasmid-based mobilization assay.
• Analysis of Alu sequence and RNA-protein complex formation with SRP9/14.

Main Results:

• Functionally intact core Alu elements are highly abundant, outnumbering other active transposons in humans.
• Active Alu copies are present in multiple lineages, including modern AluY and most AluS subfamilies.
• Alu activity is determined by both the primary sequence of the Alu copy and its interaction with SRP9/14 to form ribonucleoprotein (RNP) complexes.

Conclusions:

• Alu elements represent the most significant transposon-mediated mutagenic risk to the human genome.
• The study provides a foundation for identifying specific Alu copies likely to cause genetic variation and diseases.
• Understanding Alu activity is crucial for comprehending genome instability and inherited diseases.