Recognition and
cleavage of primary microRNA precursors by the nuclear processing enzyme Drosha
Authurs
: Yan Zeng, Rui Yi and Bryan R Cullen
Source: The EMBO Journal advance online publication,
Speaker: 李松洲
Advisor: 林文昌 副教授
Date:
Abstract:
A critical step during
human microRNA maturation is the processing of the primary microRNA transcript
by the nuclear RNaseIII enzyme Drosha to generate the ~60-nucleotide precursor
microRNA hairpin. How Drosha recognizes primary RNA substrates and selects its
cleavage sites has remained a mystery, especially given that the known targets
for Drosha processing show no discernable sequence homology. Here, we show that
human Drosha selectively cleaves RNA hairpins bearing a large (X10 nucleotides)
terminal loop. From the junction of the loop and the adjacent stem, Drosha then
cleaves approximately two helical RNA turns into the stem to produce the
precursor microRNA. Beyond the precursor microRNA cleavage sites, approximately
one helix turn of stem extension is also essential for efficient processing.
While the sites of Drosha cleavage are determined largely by the distance from
the terminal loop, variations in stem structure and sequence around the
cleavage site can fine-tune the actual cleavage sites chosen.
1. Raouf Alami et al Anti-bs-Ribozyme
Reduces bs mRNA Levels in Transgenic Mice: Potential Application to the Gene
Therapy of Sickle Cell Anemia Blood Cells,
Molecules, and Diseases 1999,25:110
2. Peter Nelson et al : The microRNA world: small is
mighty. TRENDS in Biochemical Science
2003, 128:
3. Eric C Lai et al.
Computational identification of Drosophila
microRNA genes. Genome Biology
2003,4:R42