Microprocessor Recruitment to Elongating RNA Polymerase II Is Required for Differential Expression of MicroRNAs
The cellular abundance of mature microRNAs (miRNAs) is dictated by the efficiency of nuclear processing of primary miRNA transcripts (pri-miRNAs) into pre-miRNA intermediates. The Microprocessor complex of Drosha and DGCR8 carries this out, but it has been unclear what controls Microprocessor’s diff...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-09-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717312718 |
| _version_ | 1818025493123825664 |
|---|---|
| author | Victoria A. Church Sigal Pressman Mamiko Isaji Mary Truscott Nihal Terzi Cizmecioglu Stephen Buratowski Maxim V. Frolov Richard W. Carthew |
| author_facet | Victoria A. Church Sigal Pressman Mamiko Isaji Mary Truscott Nihal Terzi Cizmecioglu Stephen Buratowski Maxim V. Frolov Richard W. Carthew |
| author_sort | Victoria A. Church |
| collection | DOAJ |
| description | The cellular abundance of mature microRNAs (miRNAs) is dictated by the efficiency of nuclear processing of primary miRNA transcripts (pri-miRNAs) into pre-miRNA intermediates. The Microprocessor complex of Drosha and DGCR8 carries this out, but it has been unclear what controls Microprocessor’s differential processing of various pri-miRNAs. Here, we show that Drosophila DGCR8 (Pasha) directly associates with the C-terminal domain of the RNA polymerase II elongation complex when it is phosphorylated by the Cdk9 kinase (pTEFb). When association is blocked by loss of Cdk9 activity, a global change in pri-miRNA processing is detected. Processing of pri-miRNAs with a UGU sequence motif in their apical junction domain increases, while processing of pri-miRNAs lacking this motif decreases. Therefore, phosphorylation of RNA polymerase II recruits Microprocessor for co-transcriptional processing of non-UGU pri-miRNAs that would otherwise be poorly processed. In contrast, UGU-positive pri-miRNAs are robustly processed by Microprocessor independent of RNA polymerase association. |
| first_indexed | 2024-12-10T04:16:59Z |
| format | Article |
| id | doaj.art-18f0c1c2733240598accbdfcb27f21a8 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-10T04:16:59Z |
| publishDate | 2017-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-18f0c1c2733240598accbdfcb27f21a82022-12-22T02:02:34ZengElsevierCell Reports2211-12472017-09-0120133123313410.1016/j.celrep.2017.09.010Microprocessor Recruitment to Elongating RNA Polymerase II Is Required for Differential Expression of MicroRNAsVictoria A. Church0Sigal Pressman1Mamiko Isaji2Mary Truscott3Nihal Terzi Cizmecioglu4Stephen Buratowski5Maxim V. Frolov6Richard W. Carthew7Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USADepartment of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USADepartment of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USADepartment of Biochemistry and Molecular Genetics, University of Illinois, Chicago, IL 60607, USADepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USADepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USADepartment of Biochemistry and Molecular Genetics, University of Illinois, Chicago, IL 60607, USADepartment of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USAThe cellular abundance of mature microRNAs (miRNAs) is dictated by the efficiency of nuclear processing of primary miRNA transcripts (pri-miRNAs) into pre-miRNA intermediates. The Microprocessor complex of Drosha and DGCR8 carries this out, but it has been unclear what controls Microprocessor’s differential processing of various pri-miRNAs. Here, we show that Drosophila DGCR8 (Pasha) directly associates with the C-terminal domain of the RNA polymerase II elongation complex when it is phosphorylated by the Cdk9 kinase (pTEFb). When association is blocked by loss of Cdk9 activity, a global change in pri-miRNA processing is detected. Processing of pri-miRNAs with a UGU sequence motif in their apical junction domain increases, while processing of pri-miRNAs lacking this motif decreases. Therefore, phosphorylation of RNA polymerase II recruits Microprocessor for co-transcriptional processing of non-UGU pri-miRNAs that would otherwise be poorly processed. In contrast, UGU-positive pri-miRNAs are robustly processed by Microprocessor independent of RNA polymerase association.http://www.sciencedirect.com/science/article/pii/S2211124717312718DrosophilamicroRNARNA polymerase IIDGCR8 |
| spellingShingle | Victoria A. Church Sigal Pressman Mamiko Isaji Mary Truscott Nihal Terzi Cizmecioglu Stephen Buratowski Maxim V. Frolov Richard W. Carthew Microprocessor Recruitment to Elongating RNA Polymerase II Is Required for Differential Expression of MicroRNAs Cell Reports Drosophila microRNA RNA polymerase II DGCR8 |
| title | Microprocessor Recruitment to Elongating RNA Polymerase II Is Required for Differential Expression of MicroRNAs |
| title_full | Microprocessor Recruitment to Elongating RNA Polymerase II Is Required for Differential Expression of MicroRNAs |
| title_fullStr | Microprocessor Recruitment to Elongating RNA Polymerase II Is Required for Differential Expression of MicroRNAs |
| title_full_unstemmed | Microprocessor Recruitment to Elongating RNA Polymerase II Is Required for Differential Expression of MicroRNAs |
| title_short | Microprocessor Recruitment to Elongating RNA Polymerase II Is Required for Differential Expression of MicroRNAs |
| title_sort | microprocessor recruitment to elongating rna polymerase ii is required for differential expression of micrornas |
| topic | Drosophila microRNA RNA polymerase II DGCR8 |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717312718 |
| work_keys_str_mv | AT victoriaachurch microprocessorrecruitmenttoelongatingrnapolymeraseiiisrequiredfordifferentialexpressionofmicrornas AT sigalpressman microprocessorrecruitmenttoelongatingrnapolymeraseiiisrequiredfordifferentialexpressionofmicrornas AT mamikoisaji microprocessorrecruitmenttoelongatingrnapolymeraseiiisrequiredfordifferentialexpressionofmicrornas AT marytruscott microprocessorrecruitmenttoelongatingrnapolymeraseiiisrequiredfordifferentialexpressionofmicrornas AT nihalterzicizmecioglu microprocessorrecruitmenttoelongatingrnapolymeraseiiisrequiredfordifferentialexpressionofmicrornas AT stephenburatowski microprocessorrecruitmenttoelongatingrnapolymeraseiiisrequiredfordifferentialexpressionofmicrornas AT maximvfrolov microprocessorrecruitmenttoelongatingrnapolymeraseiiisrequiredfordifferentialexpressionofmicrornas AT richardwcarthew microprocessorrecruitmenttoelongatingrnapolymeraseiiisrequiredfordifferentialexpressionofmicrornas |