Transcription elongation and human disease

Joan Weliky Conaway, Ronald C. Conaway

Research output: Contribution to journalReview articlepeer-review

74 Scopus citations

Abstract

Eukaryotic mRNA synthesis is catalyzed by multisubunit RNA polymerase II and proceeds through multiple stages referred to as preinitiation, initiation, elongation, and termination. Over the past 20 years, biochemical studies of eukaryotic mRNA synthesis have largely focused on the preinitiation and initiation stages of transcription. These studies led to the discovery of the class of general initiation factors (TFIIB, TFIID, TFIIE, TFIIF, and TFIIH), which function in intimate association with RNA polymerase II and are required for selective binding of polymerase to its promoters, formation of the open complex, and synthesis of the first few phosphodiester bonds of nascent transcripts. Recently, biochemical studies of the elongation stage of eukaryotic mRNA synthesis have led to the discovery of several cellular proteins that have properties expected of general elongation factors and that have been found to play unanticipated roles in human disease. Among these candidate general elongation factors are the positive transcription elongation factor b (P-TEFb), eleven-nineteen lysine- rich in leukemia (ELL), Cockayne syndrome complementation group B (CSB), and elongin proteins, which all function in vitro to expedite elongation by RNA polymerase II by suppressing transient pausing or premature arrest by polymerase through direct interactions with the elongation complex. Despite their similar activities in elongation, the P-TEFb, ELL, CSB, and elongin proteins appear to play roles in a diverse collection of human diseases, including human immunodeficiency virus-1 infection, acute myeloid leukemia, Cockayne syndrome, and the familial cancer predisposition syndrome yon Hippel-Lindau disease. Here we review our current understanding of the P- TEFb, ELL, CSB, and elongin proteins, their mechanisms of action, and their roles in human disease.

Original languageEnglish (US)
Pages (from-to)301-319
Number of pages19
JournalAnnual review of biochemistry
Volume68
DOIs
StatePublished - 1999
Externally publishedYes

Keywords

  • Acute myeloid leukemia
  • Cockayne syndrome
  • CSB
  • ELL
  • ELL2
  • Elongin
  • P-TEFb
  • RNA polymerase II
  • Von Hippel-Lindau disease

ASJC Scopus subject areas

  • Biochemistry

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