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The Diverse Active Sites in Splicing, Debranching, and MicroRNA Processing Around RNA Phosphodiester Bonds

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From Nucleic Acids Sequences to Molecular Medicine

Part of the book series: RNA Technologies ((RNATECHN))

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Abstract

The cleavage and ligation reactions at RNA phosphodiester bonds are the central reactions catalyzed by enzymes in critical cellular regulatory pathways. In pre-mRNA splicing, two phospho-transesterifications result in the right mRNA for protein synthesis with the intervening intron removed as a lariat structure. The lariat RNA is then debranched by an enzyme that specifically acts on this 2′-5′-branched RNA. Following debranching, some of these introns that include pre-microRNA sequences can be processed by Dicer that cleaves the RNA to provide microRNAs. Dicer and Drosha, enzymes that act on much bigger primary transcripts, are both RNase III-like enzymes that cleave the RNA phosphodiester linkage. All these reactions are in related pathways, and the RNA phosphodiester bonds are most likely cleaved with the aid of two metal ions, yet the active sites that host these could be composed entirely of RNA or entirely of protein, or possibly a hybrid of the two. Where unknown, it is possible to estimate some of these active site architectures through homology to closely related enzymes. Better insight into these related process and active sites will play a key role in leveraging these important RNA regulatory processes for molecular medicine.

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Abbreviations

3′-SS:

3′-splice site

5′-SS:

5′-splice site

Aa-RNase III:

Aquifex aeolicus Ribonuclease III

BP:

Branch point

BPS:

Branch point sequence

Dbr:

Debranching enzyme

ISL:

Intramolecular stem loop

mRNA:

Messenger RNA

miRNA:

MicroRNA

RISC:

RNA-induced silencing complex

RNAi:

RNA interference

RNase:

Ribonuclease

RNP:

Ribonucleoprotein

snRNA:

Small nuclear RNA

snoRNA:

Small nucleolar RNA

U2AF:

U2 auxiliary factor

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Acknowledgment

The authors thank the DSF Charitable Foundation for financial support of the Das laboratory.

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Authors and Affiliations

  1. Department of Chemistry and Center for Nucleic Acids Science and Technology, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, PA, 15213, USA

    Sourav Kumar Dey, Eduardo Paredes, Molly Evans & Subha R. Das

Authors
  1. Sourav Kumar Dey
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  2. Eduardo Paredes
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  3. Molly Evans
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  4. Subha R. Das
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Corresponding author

Correspondence to Subha R. Das .

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Editors and Affiliations

  1. Institute of Chemistry/Biochemistry, Free University Berlin, Thielallee 63, Berlin, 14195, Berlin, Germany

    Volker A. Erdmann

  2. Inst. Bioorganic Chemistry, PAN Poznan, ul. Z. Noskowskiego 12/14, Poznan, 61-704, Poland

    Jan Barciszewski

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Dey, S.K., Paredes, E., Evans, M., Das, S.R. (2012). The Diverse Active Sites in Splicing, Debranching, and MicroRNA Processing Around RNA Phosphodiester Bonds. In: Erdmann, V., Barciszewski, J. (eds) From Nucleic Acids Sequences to Molecular Medicine. RNA Technologies. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27426-8_19

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