microRNAs (miRNAs) are crucial for cellular development and homeostasis. In order to better understand regulation of miRNA biosynthesis, we studied cleavage of primary miRNAs by Drosha. While Drosha knockdown triggers an expected decrease of many mature miRNAs in human embryonic stem cells (hESC), a subset of miRNAs are not reduced. Statistical analysis of miRNA secondary structure and fold change of expression in response to Drosha knockdown showed that absence of mismatches in the central region of the hairpin, 5 and 9-12 nt from the Drosha cutting site conferred decreased sensitivity to Drosha knockdown. This suggests that, when limiting, Drosha processes miRNAs without mismatches more efficiently than mismatched miRNAs. This is important because Drosha expression changes over cellular development and the fold change of expression for miRNAs with mismatches in the central region correlates with Drosha levels. To examine the biochemical relationship directly, we overexpressed structural variants of miRNA-145, miRNA-137, miRNA-9, and miRNA-200b in HeLa cells with and without Drosha knockdown; for these miRNAs, elimination of mismatches in the central region increased, and addition of mismatches decreased their expression in an in vitro assay and in cells with low Drosha expression. Change in Drosha expression can be a biologically relevant mechanism by which eukaryotic cells control miRNA profiles. This phenomenon may explain the impact of point mutations outside the seed region of certain miRNAs.
JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact support@jstor.org.. Indiana State University and St. Louis University are collaborating with JSTOR to digitize, preserve and extend access to African American Review. A ugust Wilson granted me the following interview while he was in Washington, DC, for the November 1991 premiere of Two Trains Running at the Kennedy Center. Extremely personable and undeniably committed to his art, Wilson carefully outlined his answers to my questions about his growth from poet to playwright, about the cultural and political agendas underlying his plays, and about his role as a black writer. Shannon: Early in your career you made a gradual shift from writing poetry to writing plays. How has being a poet affected your success as a playwright? Wilson: It's the bedrock of my playwrting . . . not so much in the language as in the approach and the thinking. Thinking as a poet, one thinks differently than one thinks as a playwright. The idea of metaphor is a very large idea in my plays and something that I find lacking in most contemporary plays. I think I write the kinds of plays that I do because I have twenty-six years of writing poetry underneath all of that. Shannon: I'm fascinated by the combination of memory, history, myth-making, and the blues in your work. Do you perceive your role as an historian, as a prophet, as a healer, or perhaps as something else?Wilson: Well, I just say playwright. Of course, I use history and the historical perspective. For instance, in The Piano Lesson, you can see the actor, the character going down a road, and given the benefit of a fifty-year historical perspective, we know how all this turned out. I try to keep all of the elements of the culture alive in my work, and myth is certainly a part of it. Mythology, history, social organizations, economics-all of these things are part of the culture. I make sure that each element is in some way represented-some elements more so than others-in the plays, which I think gives them a fullness and a completeness, creates the impression that this is an entire world. Shannon: What is your reasoning behind writing a 400-year-old autobiography in ten plays? At what point did you decide upon this strategy?Wilson: Well, actually, I didn't start out with a grand idea. I wrote a play called Jitney!, set in '71, and a play called Fullerton Street that I set in '41. Then I wrote MA Rainey's Black Bottom, which I set in '27, and it was after I did that that I thought, "I've
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