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Cis-acting influences on Alu RNA levels
C Alemán1, A M Roy-Engel, T H Shaikh
1Tulane Cancer Center, SL-66, and Department of Environmental Health Sciences, Tulane University-Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
Nucleic Acids Research
|November 30, 2000
Summary
Sequence variations within human Alu elements, particularly in the right half and 3' end, significantly influence their RNA levels and retroposition capability. These individual differences may confer a selective advantage to master Alu elements.
Area of Science:
- Genetics
- Molecular Biology
- Genomics
Background:
- The human genome contains over one million copies of the Alu short interspersed repeated element (SINE).
- Alu elements amplify via retroposition, an RNA-mediated mechanism, but the factors controlling this process are not fully understood.
- The amplification rate of Alu elements has significantly decreased over the last 40 million years.
Purpose of the Study:
- To investigate how sequence variations within individual Alu elements influence their RNA expression levels.
- To determine the impact of internal sequence variations and 3' flanking sequences on Alu RNA steady-state levels.
- To identify features that may contribute to the selective advantage of actively amplifying Alu elements.
Main Methods:
- Cultured cells were used to assess the steady-state levels of full-length Alu RNA.
- Analysis of Alu subfamily diagnostic mutations and random mutations in the right half of Alu elements.
- Evaluation of sequence variations at the 3' unique end of Alu transcripts.
Main Results:
- Alu subfamily diagnostic mutations did not significantly affect Alu RNA levels.
- Random mutations in the right half of Alu elements altered their RNA steady-state levels.
- Sequence variations at the 3' end of the transcript significantly impacted Alu RNA levels.
Conclusions:
- Sequence mutations and variations in 3' end sequences are key contributors to Alu RNA levels.
- These sequence differences suggest that actively amplifying 'master' Alu elements possess individual variations that provide a selective advantage.
- Understanding these variations is crucial for comprehending Alu element amplification and retroposition dynamics.