The Alu element has been a major source of new exons during primate evolution. 
Thousands of human genes contain spliced exons derived from Alu elements. 
However, identifying Alu exons that have acquired genuine biological functions 
remains a major challenge. We investigated the creation and establishment of Alu 
exons in human genes, using transcriptome profiles of human tissues generated by 
high-throughput RNA sequencing (RNA-Seq) combined with extensive RT-PCR 
analysis. More than 25% of Alu exons analyzed by RNA-Seq have estimated 
transcript inclusion levels of at least 50% in the human cerebellum, indicating 
widespread establishment of Alu exons in human genes. Genes encoding zinc finger 
transcription factors have significantly higher levels of Alu exonization. 
Importantly, Alu exons with high splicing activities are strongly enriched in 
the 5'-UTR, and two-thirds (10/15) of 5'-UTR Alu exons tested by luciferase 
reporter assays significantly alter mRNA translational efficiency. Mutational 
analysis reveals the specific molecular mechanisms by which newly created 5'-UTR 
Alu exons modulate translational efficiency, such as the creation or elongation 
of upstream ORFs that repress the translation of the primary ORFs. This study 
presents genomic evidence that a major functional consequence of Alu exonization 
is the lineage-specific evolution of translational regulation. Moreover, the 
preferential creation and establishment of Alu exons in zinc finger genes 
suggest that Alu exonization may have globally affected the evolution of primate 
and human transcriptomes by regulating the protein production of master 
transcriptional regulators in specific lineages.