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Splice Now or Splice Later

Cells often multi-task when synthesizing and splicing RNA. But when unconventional splicing is required, they synthesize first and splice later, according to a recent study.

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NEWARK, N.J. - Cells often multi-task when synthesizing and splicing RNA. But when unconventional splicing is required, they synthesize first and splice later, according to a study led by researchers at the Public Health Research Institute of UMDNJ-New Jersey Medical School and published in Cell on November 23.

Proteins are made from genetic material called ribonucleic acid, or RNA. Each piece of RNA is made up of alternating stretches of useful and useless genetic material called “exons” and “introns,” respectively. To make a functional protein, the cell must get rid of the introns and link the exons together in a process called splicing. To ensure that splicing occurs in an orderly fashion, many RNAs are spliced as they are being synthesized from their DNA templates (“co-transcriptionally”).

In some cases, however, the cell skips exons or stitches them together in a different order, thus producing a distinct protein. Prior studies showed that this ‘alternative splicing’ can be achieved by slowing down the transcription process enough to allow multiple introns and exons to be made before splicing occurs.

Sanjay Tyagi, Ph.D., and colleagues at UMDNJ-New Jersey Medical School used a clever new imaging technique to follow the fate of individual RNA molecules inside the cell. RNAs that follow the usual splicing rules were spliced co-transcriptionally. But for two alternatively spliced RNAs, the splicing process was delayed until transcription was complete and the RNA was floating free. Whether this synthesize-first-splice-later approach holds true for most alternatively spliced RNAs awaits future genome-wide studies.

The University of Medicine and Dentistry of New Jersey (UMDNJ) is the nation's largest free-standing public health sciences university with more than 6,000 students attending the state's three medical schools, its only dental school, a graduate school of biomedical sciences, a school of health related professions, a school of nursing and its only school of public health on five campuses. UMDNJ operates University Hospital, a Level I Trauma Center in Newark, and University Behavioral HealthCare, which provides a continuum of healthcare services with multiple locations throughout the state.