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Science 8 August 2003:
Vol. 301. no. 5634, pp. 836 - 838
DOI: 10.1126/science.1085792
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Reports

Single Molecule Profiling of Alternative Pre-mRNA Splicing

Jun Zhu,1* Jay Shendure,1* Robi D. Mitra,2 George M. Church1{dagger}

Alternative pre-messenger RNA splicing is an important mechanism for generating protein diversity and may explain in part how mammalian complexity arises from a surprisingly small complement of genes. Here, we describe "digital polony exon profiling,"a single molecule–based technology for studying complex alternative pre-messenger RNA splicing. This technology allows researchers to monitor the combinatorial diversity of exon inclusion in individual transcripts. A minisequencing strategy provides single nucleotide resolution, and the digital nature of the technology allows quantitation of individual splicing variants. Digital polony exon profiling can be used to investigate the physiological and pathological roles of alternately spliced messenger RNAs, as well as the mechanisms by which these messenger RNAs are produced.

1 Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
2 Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.



* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: church{at}arep.med.harvard.edu

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