The factors regulating the expression of microRNAs (miRNAs), a ubiquitous family 
of approximately 22-nt noncoding regulatory RNAs, remain undefined. However, it 
is known that miRNAs are first transcribed as a largely unstructured precursor, 
termed a primary miRNA (pri-miRNA), which is sequentially processed in the 
nucleus, to give the approximately 65-nt pre-miRNA hairpin intermediate, and 
then in the cytoplasm, to give the mature miRNA. Here we have sought to identify 
the RNA polymerase responsible for miRNA transcription and to define the 
structure of a full-length human miRNA. We show that the pri-miRNA precursors 
for nine human miRNAs are both capped and polyadenylated and report the sequence 
of the full-length, approximately 3433-nt pri-miR-21 RNA. This pri-miR-21 gene 
sequence is flanked 5' by a promoter element able to transcribe heterologous 
mRNAs and 3' by a consensus polyadenylation sequence. Nuclear processing of 
pri-miRNAs was found to be efficient, thus largely preventing the nuclear export 
of full-length pri-miRNAs. Nevertheless, an intact miRNA stem-loop precursor 
located in the 3' UTR of a protein coding gene only moderately inhibited 
expression of the linked open reading frame, probably because the 3' truncated 
mRNA could still be exported and expressed. Together, these data show that human 
pri-miRNAs are not only structurally similar to mRNAs but can, in fact, function 
both as pri-miRNAs and mRNAs.