skip to content »

Molecular and Human Genetics

Houston, Texas

Department of Molecular and Human Genetics
Department of Molecular and Human Genetics
not shown on screen

Richard L. Kelley, Ph.D.

Richard L. Kelley, Ph.D.

Associate Professor, Department of Molecular and Human Genetics

Other Positions

Associate Professor, Department of Molecular & Cellular Biology; Program in Developmental Biology
Co-Director, Program in Developmental Biology

Education

B.S., University of Texas, Arlington, 1979
Ph.D., Stanford University, 1984
Postdoc, Embryology, Carnegie Institution of Washington, 1987

Research Interests

Noncoding RNAs and chromatin structure

A major surprise over the last ten years has been the discovery of many diverse roles of noncoding RNAs. Several families of small (21-25 nt) RNAs mediate gene silencing through RNAi-like mechanisms or translational control. Noncoding RNAs are produced in most imprinted loci in mammals, although their functions remain a mystery. Larger RNAs such as Xist in mammals and roX in flies paint entire X chromosomes to somehow target chromatin remodeling enzymes to the correct chromosome. My research program exploits the many genetic, molecular, and cytological advantages of Drosophila to understand how the roX RNAs direct the dosage compensation machinery to the male X chromosome.

Flies have two different roX RNAs. The genes producing roX1 and roX2 both map to the X chromosome, and their RNA products “paint” the 21 Mbp euchromatic portion of the male X in a reproducible pattern of hundreds of bands when complexed with the 5 known MSL proteins. Some of the MSL proteins are histone modifying enzymes which alter the chromatin architecture allowing a two-fold increase in transcription from thousands of unrelated genes linked on the male X chromosome. One of the primary functions of the roX RNA seems to be targeting these chromatin remodeling enzymes to the correct sites in the genome. The two roX RNAs are very different in size (3.7 vs. 0.6 kb) and have almost no primary sequence in common, and yet are functionally redundant. Males can survive with only roX1 or only roX2 but die if both genes are mutated. Females are unaffected my mutations in roX genes or msl genes because they do not hypertranscribe their two X chromosomes.

We are currently testing a model that postulates that the MSL complex spreads epigenetically from sites of roX transcription. We now understand the factors that control local spreading along a chromosome, but the question being asked is whether this serves to deliver the MSL complex to target genes along the X, or perhaps some other autoregulatory function controlling roX transcription.

Selected Publications

MSL Complex

The Drosophila dosage compensation complex (red) can be misdirected to an autosome by moving the gene for the noncoding roX RNA.

  1. Kelley RL, Lee OK, Shim YK (2008). Transcription rate of noncoding roX1 RNA controls local spreading of the Drosophila MSL chromatin remodeling complex. Mech. Dev. 125(11-12): 1009-19. [Pub Med]
  2. Kelley RL (2004). Path to equality strewn with roX. Dev. Biol. 269(1): 18-25 (Review). [Pub Med]
  3. Kelley RL, Kuroda MI (2003). The Drosophila roX1 RNA gene can overcome silent chromatin by recruiting the male-specific lethal dosage compensation complex. Genetics 164(2): 565-74. [Pub Med]
  4. Park Y, Kelley RL, Oh H, Kuroda MI, Meller VH (2002). Extent of chromatin spreading determined by roX RNA recruitment of MSL proteins. Science 298(5598): 1620-3. [Pub Med]
  5. Kageyama Y, Mengus G, Gilfillan G, Kennedy HG, Stuckenholz C, Kelley RL, Becker PB, Kuroda MI (2001). Association and spreading of the Drosophila dosage compensation complex from a discrete roX1 chromatin entry site. EMBO J. 20(9): 2236-45. [Pub Med]
  6. Meller VH, Gordadze PR, Park Y, Chu X, Stuckenholz C, Kelley RL, Kuroda MI (2000). Ordered assembly of roX RNAs into MSL complexes on the dosage-compensated X chromosome in Drosophila. Curr. Biol. 10(3): 136-43. [Pub Med]
  7. Kelley RL, Meller VH, Gordadze PR, Roman G, Davis RL, Kuroda MI (1999). Epigenetic spreading of the Drosophila dosage compensation complex from roX RNA genes into flanking chromatin. Cell 98(4): 513-22. [Pub Med]

More Publications (PubMed)

Contact Information:

Richard Kelley, Ph.D
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza, MS BCM225
Houston, TX, 77030, U.S.A.

Phone: 713-798-4526
Fax: 713-798-8515
E-mail:

E-mail this page to a friend