Molecular Basis for the Recognition of Primary microRNAs by the Drosha-DGCR8 Complex

Han, Jinju; Lee, Yoontae; Yeom, Kyu Hyeon; Nam, Jin Wu; Heo, Inha; Rhee, Je-Keun; Sohn, Sung-Hwa; Cho, Yunje; Zhang, Byoung Tak; Kim, V. Narry

doi:10.1016/j.cell.2006.03.043

Cited by 1,363 publications

(1,317 citation statements)

References 45 publications

Supporting

Mentioning

1,250

Contrasting

Unclassified

Order By: Relevance

“…2A). Although a previous study showed that the pri-miRNA loop is dispensable for miRNA processing in vitro (Han et al, 2006), our results strongly suggest that terminal loop nucleotides play a key role in Drosha/DGCR8 proces-sing of pri-miRNA to pre-miRNA in vivo.…”

Section: A B Ccontrasting

confidence: 83%

“…Intriguingly, there are controversial roles for pri-miRNA loops in miRNA processing and mature miRNA biogenesis. Previously, a mir-16-1 in vitro processing assay suggested that the loop is dispensable for pri-mir-16-1 processing and mature miR-16 production (Han et al, 2006). However, Zhang and Zeng (2010) reported that a flexible terminal loop region is critical for miRNA processing, using a similar in vitro processing assay for different miRNAs.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of Loop Nucleotide Polymorphisms Affecting MicroRNA Processing and Function

Xiong

Kang

Zheng

et al. 2013

Molecules and Cells

View full text Add to dashboard Cite

MicroRNAs are short 21-22 nucleotide single strand RNAs that are involved in post-transcriptional regulation of gene expression. Most microRNAs are first transcribed as long primary microRNAs and then undergo a two step-wise sequential processing to yield single-stranded mature microRNAs. It has been suggested that the loop region of primary microRNAs plays an important role in regulating microRNA biogenesis and target recognition. However, despite the fact that several single nucleotide polymorphisms have been identified in mature microRNA sequences and are related to human diseases, it remains unclear whether and how the single nucleotide polymorphisms in the loop regions of primary microRNAs would affect the biogenesis and function of microRNAs. Herein, we provide evidence that primary microRNAs loop nucleotides control the accuracy and efficiency of microRNA processing. Accordingly, we identified 32 single nucleotide polymorphisms in the loop regions of human primary microRNAs using bioinformatics, and further validated three loss-of-function and one gain-of-function single nucleotide polymorphisms using dual-luciferase assays. Thus, these results reveal a critical regulatory role encoded in the loop nucleotides of primary microRNAs for microRNA processing and function.

show abstract

Section: A B Ccontrasting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Identification of Loop Nucleotide Polymorphisms Affecting MicroRNA Processing and Function

Xiong

Kang

Zheng

et al. 2013

Molecules and Cells

View full text Add to dashboard Cite

show abstract

“…Both cell culture experiments and in vitro Drosha cleavage assays have shown that, for processing to occur, an extension of several base-paired residues is required beyond the final pre-miRNA product (Lee et al, 2003;Zeng and Cullen, 2003). Furthermore, a flanking, single-stranded RNA is required for efficient processing in vitro Han et al, 2006). At the other end of the hairpin, a large terminal loop (>10 nt) is preferred by Drosha .…”

Section: Production Of Mirna Precursors In Animal Cellsmentioning

confidence: 99%

Principles of micro-RNA production and maturation

2006

View full text Add to dashboard Cite

Micro-RNAs (miRNAs) are a class of approximately 22-nucleotide non-coding RNAs expressed in multicellular organisms. They are first transcribed in a similar manner to pre-mRNAs. The transcripts then go through a series of processing steps, including endonucleolytic cleavage, nuclear export and a strand selection procedure, to yield the single-stranded mature miRNA products. The transcription and processing of miRNAs determines the abundance and the sequence of mature miRNAs and has important implications for the function of miRNAs.

show abstract

“…12,13,16 It independently binds to pri-miRNAs [17][18][19] and makes a major contribution to their recognition by the processing machinery. In addition, proper control of DGCR8 expression and activity appears to be important for normal miRNA biogenesis.…”

mentioning

confidence: 99%

Structure of the dimerization domain of DiGeorge Critical Region 8

et al. 2010

View full text Add to dashboard Cite

Maturation of microRNAs (miRNAs,~22nt) from long primary transcripts [primary miRNAs (pri-miRNAs)] is regulated during development and is altered in diseases such as cancer. The first processing step is a cleavage mediated by the Microprocessor complex containing the Drosha nuclease and the RNA-binding protein DiGeorge critical region 8 (DGCR8). We previously reported that dimeric DGCR8 binds heme and that the heme-bound DGCR8 is more active than the heme-free form. Here, we identified a conserved dimerization domain in DGCR8. Our crystal structure of this domain (residues 298-352) at 1.7 Å resolution demonstrates a previously unknown use of a WW motif as a platform for extensive dimerization interactions. The dimerization domain of DGCR8 is embedded in an independently folded heme-binding domain and directly contributes to association with heme. Heme-binding-deficient DGCR8 mutants have reduced pri-miRNA processing activity in vitro. Our study provides structural and biochemical bases for understanding how dimerization and heme binding of DGCR8 may contribute to regulation of miRNA biogenesis.

show abstract

Molecular Basis for the Recognition of Primary microRNAs by the Drosha-DGCR8 Complex

Cited by 1,363 publications

References 45 publications

Identification of Loop Nucleotide Polymorphisms Affecting MicroRNA Processing and Function

Identification of Loop Nucleotide Polymorphisms Affecting MicroRNA Processing and Function

Principles of micro-RNA production and maturation

Structure of the dimerization domain of DiGeorge Critical Region 8

Contact Info

Product

Resources

About