Conservation of the heterochronic regulator Lin-28, its developmental expression and microRNA complementary sites
Abstract
The heterochronic gene lin-28 is a regulator of developmental timing in the nematode Caenorhabditis elegans. It must be expressed in the first larval stage and downregulated by the second stage for normal development. This downregulation is mediated in part by lin-4, a 21-nt microRNA. If downregulation fails due to a mutation in a short sequence in the lin-28 3' UTR that is complementary to lin-4, then a variety of somatic cell lineages fail to progress normally in development. Here, we report that Lin-28 homologues exist in diverse animals, including Drosophila, Xenopus, mouse, and human. These homologues are characterized by the LIN-28 protein's unusual pairing of RNA-binding motifs: a cold shock domain (CSD) and a pair of retroviral-type CCHC zinc knuckles. Conservation of LIN-28 proteins shows them to be distinct from the other conserved family of CSD-containing proteins of animals, the Y-box proteins. Importantly, the LIN-28 proteins of Drosophila, Xenopus, and mouse each appear to be expressed and downregulated during development, consistent with a conserved role for this regulator of developmental timing. In addition, the extremely long 3' UTRs of mouse and human Lin-28 genes show extensive regions of sequence identity that contain sites complementary to the mammalian homologues of C. elegans lin-4 and let-7 microRNAs, suggesting that microRNA regulation is a conserved feature of the Lin-28 gene in diverse animals.
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LIN-28 is present in undifferentiated P19 and NT2/D1 cells, but it is not detected in neuronal or liver tissues.
“Interestingly, LIN-28 is present in undifferentiated P19 and NT2/D1 cells, but it is not detected in neuronal or liver tissues [46].”
From Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation (2004) · cites this paper as [46]
The 3' UTRs of the mouse and human Lin-28 mRNAs contain conserved sequences complementary to miR-125b, let-7a, and miR-218.
“The 3' UTRs of the mouse and human Lin-28 mRNAs contain conserved sequences complementary to miR-125b, let-7a, and miR-218 (Figure 5) [46]”
From Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation (2004) · cites this paper as [46]
These conserved sequences are consistent with a role for miR-125b, let-7a, and miR-218 in the downregulation of LIN-28 in NT2/D1 and P19 cells.
“consistent with a role for these miRNAs in the downregulation of LIN-28 in NT2/D1 and P19 cells.”
From Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation (2004) · cites this paper as [46]
In mammals, LIN-28 protein is downregulated as embryonic development progresses, consistent with a possible conserved role in developmental timing.
“In mammals, LIN-28 protein is downregulated as embryonic development progresses, consistent with a possible conserved role in developmental timing [46].”
From Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation (2004) · cites this paper as [46]
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- Authors
- Moss, E. G., & Tang, L.
- Venue
- Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2003-06
- Volume
- 258
- Issue
- 2
- Pages
- 432-442
- ISSN
- 0012-1606
- Cited by
- 293
- References
- 3
- Language
- en
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