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(Circulation Research. 2009;104:1327.)
© 2009 American Heart Association, Inc.

Editorials

Dysregulation of Positive Transcription Elongation Factor b and Myocardial Hypertrophy

Andrew P. Rice

From the Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Tex.

Correspondence to Dr Andrew P. Rice, Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. E-mail arice@bcm.tmc.edu

See related articles, pages 1347–1354

Key Words: hypertrophy • P-TEFb • CLP-1 • HEXIM1

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
Prolonged stimulus of the adult heart by hypertension, arrhythmias, or other pathogenic conditions can result in myocardial hypertrophy and subsequently heart failure. Hypertrophy is characterized by an increase in the size of cardiomyocytes and this is associated with an elevated rate of RNA synthesis and protein synthesis in these cells. Although mechanisms responsible for this increased RNA and protein synthesis remain to be fully elucidated, an article by Espinoza-Derout et al¹ in this issue of Circulation Research provides additional evidence that dysregulation of the general RNA polymerase II elongation factor known as P-TEFb can be an important mechanism in the development of hypertrophy.

	Regulation of RNA Polymerase II Elongation

 
RNA polymerase II transcribes all protein-coding genes, and its function is regulated both at the levels of transcription initiation and elongation. Initiation is positively regulated by transcription factors that bind to specific cis-regulatory sequences in the promoters of individual genes. These transcription factors function to recruit both coactivators and the RNA polymerase II complex and transcription initiation is enhanced at these genes. After initiation, transcriptional elongation can be defective because of the action of 2 negative factors, DSIF and NELF, which limit elongation.^2,3 These negative factors may function as a quality control mechanism to ensure capping of nascent mRNA, thereby stabilizing the RNA for subsequent processing events and transcriptional termination.⁴ Although almost all protein-coding genes appear to undergo some level of constitutive transcription initiation, only a subset actually produce full-length transcripts, indicating that many genes are defective in transcriptional elongation.⁵ This block to productive elongation is . . . [Full Text of this Article]

Related Article:

Positive Transcription Elongation Factor b Activity in Compensatory Myocardial Hypertrophy is Regulated by Cardiac Lineage Protein-1

Jorge Espinoza-Derout, Michael Wagner, Louis Salciccioli, Jason M. Lazar, Sikha Bhaduri, Eduardo Mascareno, Brahim Chaqour, and M.A.Q. Siddiqui
Circ. Res. 2009 104: 1347-1354. [Abstract] [Full Text] [PDF]