Uncoupling ribosome biogenesis regulation from RNA polymerase I activity during herpes simplex virus type 1 infection

Abstract

The ribosome is the central effector of protein synthesis, and its synthesis is intimately coordinated with that of proteins. At present, the most documented way to modulate ribosome biogenesis involves control of rDNA transcription by RNA polymerase I (RNA Pol I). Here we show that after infection of human cells with herpes simplex virus type 1 (HSV-1) the rate of ribosome biogenesis is modulated independently of RNA Pol I activity by a dramatic change in the rRNA maturation pathway. This process permits control of the ribosome biogenesis rate, giving the possibility of escaping ribosomal stress and eventually allowing assembly of specialized kinds of ribosomes.

Lytic Reactivation of the Kaposi’s Sarcoma-Associated Herpesvirus (KSHV) Is Accompanied by Major Nucleolar Alterations

“…Using different approaches, we show rRNA levels do not change during the lytic cycle. This finding is in line with previous reports in HSV-1, describing continuous association of UBF with rDNA along with colocalization with the largest RNA pol I subunit RPA43 [44], and ongoing pre-rRNA synthesis at a rate only slightly below that in uninfected cells [48]. However, unlike HSV-1 infection [48], we did not document an altered rRNA maturation pathway during the lytic cycle.…”

“…This finding is in line with previous reports in HSV-1, describing continuous association of UBF with rDNA along with colocalization with the largest RNA pol I subunit RPA43 [44], and ongoing pre-rRNA synthesis at a rate only slightly below that in uninfected cells [48]. However, unlike HSV-1 infection [48], we did not document an altered rRNA maturation pathway during the lytic cycle. Alternative modifications that may affect the turn-over of rRNAs, translation efficiency, accuracy and termination, may also alter the subsets of mRNAs targeted for translation and thus provide an additional layer of infection control.…”

“…In addition, no accumulation of the selected pre-rRNA intermediates was found by Northern blot analysis, suggesting that the proper processing of pre-rRNA continued (Figure 7). Significantly, unique rRNA processing products were previously identified in HSV-1 infected cells during lytic infection [48]. However, no unique products were identified here, and no significant differences in the relative expression levels of the different processing products were detected.…”

Lytic Reactivation of the Kaposi’s Sarcoma-Associated Herpesvirus (KSHV) Is Accompanied by Major Nucleolar Alterations

“…Using different approaches, we show rRNA levels do not change during the lytic cycle. This finding is in line with previous reports in HSV-1, describing continuous association of UBF with rDNA along with colocalization with the largest RNA pol I subunit RPA43 [44], and ongoing pre-rRNA synthesis at a rate only slightly below that in uninfected cells [48]. However, unlike HSV-1 infection [48], we did not document an altered rRNA maturation pathway during the lytic cycle.…”

“…This finding is in line with previous reports in HSV-1, describing continuous association of UBF with rDNA along with colocalization with the largest RNA pol I subunit RPA43 [44], and ongoing pre-rRNA synthesis at a rate only slightly below that in uninfected cells [48]. However, unlike HSV-1 infection [48], we did not document an altered rRNA maturation pathway during the lytic cycle. Alternative modifications that may affect the turn-over of rRNAs, translation efficiency, accuracy and termination, may also alter the subsets of mRNAs targeted for translation and thus provide an additional layer of infection control.…”

“…In addition, no accumulation of the selected pre-rRNA intermediates was found by Northern blot analysis, suggesting that the proper processing of pre-rRNA continued (Figure 7). Significantly, unique rRNA processing products were previously identified in HSV-1 infected cells during lytic infection [48]. However, no unique products were identified here, and no significant differences in the relative expression levels of the different processing products were detected.…”

Lytic Reactivation of the Kaposi’s sarcoma-associated herpesvirus (KSHV) is Accompanied by Major Nucleolar Alterations

“…Using different approaches, we show that rRNA synthesis continues during the lytic cycle. This finding is in line with previous reports in HSV-1, describing continuous association of UBF with rDNA along with colocalization with the largest RNA pol I subunit RPA43 [43], and ongoing pre-rRNA synthesis at a rate only slightly below that in uninfected cells [47]. However, unlike HSV-1 infection [47], we did not document an altered rRNA maturation pathway during the lytic cycle.…”

“…This finding is in line with previous reports in HSV-1, describing continuous association of UBF with rDNA along with colocalization with the largest RNA pol I subunit RPA43 [43], and ongoing pre-rRNA synthesis at a rate only slightly below that in uninfected cells [47]. However, unlike HSV-1 infection [47], we did not document an altered rRNA maturation pathway during the lytic cycle. In view of the ongoing rRNA transcription, alternative modifications that may affect translation efficiency, accuracy and termination, but may also alter the subsets of mRNAs targeted for translation, may provide an additional layer of infection control.…”

Lytic Reactivation of the Kaposi’s Sarcoma-Associated Herpesvirus (KSHV) Is Accompanied by Major Nucleolar Alterations

“…Using different approaches, we show rRNA levels do not change during the lytic cycle. This finding is in line with previous reports in HSV-1, describing continuous association of UBF with rDNA along with colocalization with the largest RNA pol I subunit RPA43 [44], and ongoing pre-rRNA synthesis at a rate only slightly below that in uninfected cells [48]. However, unlike HSV-1 infection [48], we did not document an altered rRNA maturation pathway during the lytic cycle.…”

“…This finding is in line with previous reports in HSV-1, describing continuous association of UBF with rDNA along with colocalization with the largest RNA pol I subunit RPA43 [44], and ongoing pre-rRNA synthesis at a rate only slightly below that in uninfected cells [48]. However, unlike HSV-1 infection [48], we did not document an altered rRNA maturation pathway during the lytic cycle. Alternative modifications that may affect the turn-over of rRNAs, translation efficiency, accuracy and termination, may also alter the subsets of mRNAs targeted for translation and thus provide an additional layer of infection control.…”

“…In addition, no accumulation of the selected pre-rRNA intermediates was found by Northern blot analysis, suggesting that the proper processing of pre-rRNA continued (Figure 7). Significantly, unique rRNA processing products were previously identified in HSV-1 infected cells during lytic infection [48]. However, no unique products were identified here, and no significant differences in the relative expression levels of the different processing products were detected.…”

Lytic Reactivation of the Kaposi’s sarcoma-associated herpesvirus (KSHV) is Accompanied by Major Nucleolar Alterations

“…Using different approaches, we show that rRNA synthesis continues during the lytic cycle. This finding is in line with previous reports in HSV-1, describing continuous association of UBF with rDNA along with colocalization with the largest RNA pol I subunit RPA43 [43], and ongoing pre-rRNA synthesis at a rate only slightly below that in uninfected cells [47]. However, unlike HSV-1 infection [47], we did not document an altered rRNA maturation pathway during the lytic cycle.…”

“…This finding is in line with previous reports in HSV-1, describing continuous association of UBF with rDNA along with colocalization with the largest RNA pol I subunit RPA43 [43], and ongoing pre-rRNA synthesis at a rate only slightly below that in uninfected cells [47]. However, unlike HSV-1 infection [47], we did not document an altered rRNA maturation pathway during the lytic cycle. In view of the ongoing rRNA transcription, alternative modifications that may affect translation efficiency, accuracy and termination, but may also alter the subsets of mRNAs targeted for translation, may provide an additional layer of infection control.…”

Lytic Reactivation of the Kaposi’s Sarcoma-Associated Herpesvirus (KSHV) Is Accompanied by Major Nucleolar Alterations

“…Using different approaches, we show rRNA levels do not change during the lytic cycle. This finding is in line with previous reports in HSV-1, describing continuous association of UBF with rDNA along with colocalization with the largest RNA pol I subunit RPA43 [44], and ongoing pre-rRNA synthesis at a rate only slightly below that in uninfected cells [48]. However, unlike HSV-1 infection [48], we did not document an altered rRNA maturation pathway during the lytic cycle.…”

“…This finding is in line with previous reports in HSV-1, describing continuous association of UBF with rDNA along with colocalization with the largest RNA pol I subunit RPA43 [44], and ongoing pre-rRNA synthesis at a rate only slightly below that in uninfected cells [48]. However, unlike HSV-1 infection [48], we did not document an altered rRNA maturation pathway during the lytic cycle. Alternative modifications that may affect the turn-over of rRNAs, translation efficiency, accuracy and termination, may also alter the subsets of mRNAs targeted for translation and thus provide an additional layer of infection control.…”

“…In addition, no accumulation of the selected pre-rRNA intermediates was found by Northern blot analysis, suggesting that the proper processing of pre-rRNA continued (Figure 7). Significantly, unique rRNA processing products were previously identified in HSV-1 infected cells during lytic infection [48]. However, no unique products were identified here, and no significant differences in the relative expression levels of the different processing products were detected.…”

Lytic Reactivation of the Kaposi’s sarcoma-associated herpesvirus (KSHV) is Accompanied by Major Nucleolar Alterations

“…Using different approaches, we show that rRNA synthesis continues during the lytic cycle. This finding is in line with previous reports in HSV-1, describing continuous association of UBF with rDNA along with colocalization with the largest RNA pol I subunit RPA43 [43], and ongoing pre-rRNA synthesis at a rate only slightly below that in uninfected cells [47]. However, unlike HSV-1 infection [47], we did not document an altered rRNA maturation pathway during the lytic cycle.…”

“…This finding is in line with previous reports in HSV-1, describing continuous association of UBF with rDNA along with colocalization with the largest RNA pol I subunit RPA43 [43], and ongoing pre-rRNA synthesis at a rate only slightly below that in uninfected cells [47]. However, unlike HSV-1 infection [47], we did not document an altered rRNA maturation pathway during the lytic cycle. In view of the ongoing rRNA transcription, alternative modifications that may affect translation efficiency, accuracy and termination, but may also alter the subsets of mRNAs targeted for translation, may provide an additional layer of infection control.…”