Relationship between viral RNAs and SC35 domains
in Raji cells and relationship among viral RNA transcript environment,
visualization of nuclear domains enriched in hnRNP K/J proteins, and
visualization of transcription sites in the EBV transcript environment
(depicted by hnRNP K/J protein immunolabeling). The approach exploring
RNA FISH (red) and immunocytochemistry has been used to establish the
relationship between viral RNAs and SC35 domains in Raji cells (A–C).
In most cells, one to three RNA accumulations are observed. With
respect to SC35 domains, RNA signals fall within three categories. As
in Namalwa cells, viral RNA is localized as either spatially distinct
(A) or associated with SC35 domains (B). However, in contrast to
Namalwa cells (see Figure 1), RNA accumulations inside the speckle
domains are often found (C). The microclusters of splicing factors
distinct from the SC35 domains at the pole of RNA accumulation are
clearly visible (insets, arrowheads). By means of RNA FISH and
immunocytochemistry, hnRNP K/J proteins (D, green) have been shown to
be highly enriched at accumulations of viral RNA (red) in
transcriptionally active Raji and Namalwa cells (E). The overlay is
documented in F. This fact has been used for the localization of
transcription sites at viral RNA accumulations. Visualization of
transcription sites (red) in the EBV transcript environment (green) is
also shown. Nuclei have been spread by osmotic shift and allowed to
transcribe de novo in the presence of modified nucleotides. RNA pol II
transcriptional competence has been restored by HeLa nuclear extract.
Because of a highly diluted nuclear content, single sites of
transcription (G–I, red) are easily distinguished. The hnRNP K/J site
(K/J site), which colocalizes with the EBV transcript environment (F),
is not disrupted by this method (G–I, green). One or two sites of
transcription (active genes) are found in the majority of K/J sites of
Namalwa spread nuclei (G and H, arrowheads). Sites of transcription
colocalize with the K/J site and are of various size, usually much
larger in Raji spread cells (I, arrowhead) than in Namalwa cells. Bars,
2 μm.